# AMR-English alignment release (generated on Mon Mar 14, 2016 at 23:18:32)
# ::id a_pmid_2234_3622.60 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Combined treatment of selumetinib and standard of care agents results in enhanced anti @-@ tumour efficacy
# ::alignments 0-1.1.1.2 1-1.1.1 2-1.1.1.1.r 3-1.1.1.1.1.1.1 4-1.1.1.1 5-1.1.1.1.2 6-1.1.1.1.2.1.r 7-1.1.1.1.2.1.1 8-1.1.1.1.2.1 9-1 10-1.2.r 11-1.2.1 12-1.2.2 14-1.2.2.1 15-1.2
(r / result-01~e.9
:ARG1 (a / and
:op1 (t / treat-04~e.1
:ARG2~e.2 (a3 / and~e.4
:op1 (s2 / small-molecule
:name (n / name :op1 "selumetinib"~e.3))
:op2 (s / standard~e.5
:mod~e.6 (a2 / agent~e.8
:mod (c / care-03~e.7))))
:ARG3-of (c2 / combine-01~e.0)))
:ARG2~e.10 (e / efficacy~e.15
:ARG1-of (e2 / enhance-01~e.11)
:mod (c3 / counter-01~e.12
:ARG1 (t2 / tumor~e.14))))
# ::id a_pmid_2234_3622.61 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Mechanistic biomarker studies of the effects of selumetinib in human tumour xenograft models have shown that , in addition to pERK1 @/@ 2 downregulation , a sustained exposure to the agent results in an increase in downstream apoptotic signalling and a decrease in cell cycle progression ( Davies et al , 2007 ) .
# ::alignments 0-1.1.2.1 1-1.1.2 2-1.1 3-1.1.1.r 5-1.1.1 6-1.1.1.1.r 7-1.1.1.1.1.1 8-1.1.1.2.r 9-1.1.1.2.2 10-1.1.1.2.1.1 11-1.1.1.2.1 12-1.1.1.2 14-1 17-1.2.2 17-1.3.1.1 18-1.2.2 18-1.3.1.1 22-1.2.2.1.1.1.1 23-1.2.2.1 26-1.2.1.2 27-1.2.1 31-1.2 32-1.2.2.r 34-1.2.2.2 35-1.2.2.2.1.r 36-1.2.2.2.1.2 37-1.2.2.2.1.1 38-1.2.2.2.1 39-1.2.2 41-1.2.2.3 42-1.2.2.3.1.r 43-1.2.2.3.1.1.1 44-1.2.2.3.1.1 45-1.2.2.3.1 48-1.3.1.1.1.1.1 50-1.3.1.1 51-1.3.1.1.2.1 54-1.3.1.2.1
(s / show-01~e.14
:ARG0 (s2 / study-01~e.2
:ARG1~e.3 (a / affect-01~e.5
:ARG0~e.6 (s3 / small-molecule
:name (n3 / name :op1 "selumetinib"~e.7))
:ARG1~e.8 (m2 / model~e.12
:mod (x / xenograft~e.11
:mod (t / tumor~e.10))
:mod (h / human~e.9)))
:mod (b / biomarker~e.1
:mod (m / mechanistic~e.0)))
:ARG1 (r / result-01~e.31
:ARG1 (e / expose-01~e.27
:ARG2 s3
:ARG1-of (s4 / sustain-01~e.26))
:ARG2~e.32 (a7 / and~e.17,18,39
:op1 (d2 / downregulate-01~e.23
:ARG1 (e2 / enzyme
:name (n / name :op1 "ERK1/2"~e.22)
:ARG3-of (p / phosphorylate-01)))
:op2 (i / increase-01~e.34
:ARG1~e.35 (s5 / signal-07~e.38
:mod (a5 / apoptosis~e.37)
:location (d4 / downstream~e.36)))
:op3 (d3 / decrease-01~e.41
:ARG1~e.42 (p2 / progress-01~e.45
:ARG1 (c / cycle-02~e.44
:ARG1 (c2 / cell~e.43))))))
:ARG1-of (d5 / describe-01
:ARG0 (p5 / publication-91
:ARG0 (a3 / and~e.17,18,50
:op1 (p3 / person
:name (n2 / name :op1 "Davies"~e.48))
:op2 (p4 / person
:mod (o / other~e.51)))
:time (d / date-entity :year 2007~e.54))))
# ::id a_pmid_2234_3622.62 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Furthermore , a chronic dosing schedule of selumetinib ( 25 mg kg @ –1 per bid for 14 doses ) in HCT @-@ 116 xenografts increased the levels of the pro @-@ apoptotic BH3 protein Bim @-@ EL (∼4 @-@ fold increase ) compared with no change with the level of this protein following a shorter dosing period ( three doses ) ( Figure 1 ) .
# ::alignments 0-1 3-1.1.1.1.3 4-1.1.1.1 5-1.1.1 7-1.1.1.1.2.1.1 9-1.1.1.1.2.2.1 10-1.1.1.1.2.2.2 11-1.1.1.1.2.2.2 15-1.1.1.1.2.2.2 15-1.1.1.1.4 18-1.1.1.1.1 19-1.1.1.1 22-1.1.5.1.1.1 24-1.1.5.1.1.1 25-1.1.5 26-1.1 28-1.1.2 29-1.1.2.1.r 31-1.1.2.1.2 33-1.1.2.1.2.1 34-1.1.2.1.3.1.1.1 35-1.1.2.1 35-1.1.2.1.3.1 36-1.1.2.1.1.1 38-1.1.2.1.1.1 41-1.1.3 42-1.1 44-1.1.4.r 46-1.1.4.1 46-1.1.4.1.r 47-1.1.4 48-1.1.4.2.r 50-1.1.4.2 51-1.1.3 53-1.1.4.2.1 54-1.1.4.3 56-1.1.4.3.1.2 56-1.1.4.3.1.2.1 56-1.1.4.3.1.2.1.r 57-1.1.4.3.1.1 58-1.1.4.3.1 60-1.1.4.3.1.3.1.1 61-1.1.4.3.1.3.1 65-1.2.1 66-1.1.1.1.4.2.1 66-1.2.1.1
(a / and~e.0
:op2 (i / increase-01~e.26,42
:ARG0 (s / schedule-01~e.5
:ARG1 (d2 / dose-01~e.4,19 :quant 14~e.18
:ARG2 (s2 / small-molecule
:name (n4 / name :op1 "selumetinib"~e.7)
:quant (c4 / concentration-quantity :quant 25~e.9
:unit (m / milligram-per-kilogram~e.10,11,15)))
:mod (c / chronic~e.3)
:frequency (r / rate-entity-91~e.15 :ARG1 2
:ARG2 (t / temporal-quantity :quant 1~e.66
:unit (d5 / day)))))
:ARG1 (l / level~e.28
:quant-of~e.29 (p / protein~e.35
:name (n2 / name :op1 "Bim-EL"~e.36,38)
:ARG0-of (f / favor-01~e.31
:ARG1 (a2 / apoptosis~e.33))
:ARG1-of (i2 / include-91
:ARG2 (p4 / protein-family~e.35
:name (n3 / name :op1 "BH3"~e.34)))))
:ARG4 (p2 / product-of~e.41,51 :op1 4)
:compared-to~e.44 (c2 / change-01~e.47 :polarity~e.46 -~e.46
:ARG1~e.48 (l2 / level~e.50
:quant-of p~e.53)
:ARG1-of (f3 / follow-01~e.54
:ARG2 (p3 / period~e.58
:time-of (d3 / dose-01~e.57)
:ARG1-of (s3 / short-07~e.56
:degree~e.56 (m2 / more~e.56))
:ARG1-of (m3 / mean-01
:ARG3 (d4 / dose-01~e.61 :quant 3~e.60)))))
:location (x / xenograft~e.25
:mod (c3 / cell-line
:name (n / name :op1 "HCT-116"~e.22,24))))
:ARG1-of (d / describe-01
:ARG0 (f2 / figure~e.65 :mod 1~e.66)))
# ::id a_pmid_2234_3622.63 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In order to exploit the apoptotic threshold of selumetinib , we wanted to study the effects of combining it with agents known to induce the apoptotic cascade to drive tumour growth inhibition and @/@ or cell death .
# ::alignments 0-1.3.r 1-1.3.r 2-1.3.r 3-1.3 5-1.3.2.2 6-1.3.2 7-1.3.2.1.r 8-1.3.2.1.1.1 10-1.1 11-1 13-1.2 15-1.2.2 16-1.2.2.1.r 17-1.2.2.1 18-1.2.2.1.1 19-1.2.2.1.2.r 20-1.2.2.1.2 21-1.2.2.1.2.1.3 23-1.2.2.1.2.1 25-1.2.2.1.2.1.1.1 26-1.2.2.1.2.1.1 28-1.2.2.1.2.1.2 29-1.2.2.1.2.1.2.2.1.1.1 30-1.2.2.1.2.1.2.2.1.1 31-1.2.2.1.2.1.2.2.1 32-1.2.2.1.2.1.2.2 34-1.2.2.1.2.1.2.2 35-1.2.2.1.2.1.2.2.2.1 36-1.2.2.1.2.1.2.2.2
(w / want-01~e.11
:ARG0 (w2 / we~e.10)
:ARG1 (s / study-01~e.13
:ARG0 w2
:ARG1 (a / affect-01~e.15
:ARG0~e.16 (c / combine-01~e.17
:ARG1 s2~e.18
:ARG2~e.19 (a2 / agent~e.20
:ARG0-of (i / induce-01~e.23
:ARG2 (c2 / cascade~e.26
:mod a3~e.25)
:purpose (d / drive-02~e.28
:ARG0 a2
:ARG1 (a4 / and-or~e.32,34
:op1 (i2 / inhibit-01~e.31
:ARG1 (g / grow-01~e.30
:ARG1 (t2 / tumor~e.29)))
:op2 (d2 / die-01~e.36
:ARG1 (c3 / cell~e.35))))
:ARG1-of (k / know-01~e.21))))))
:purpose~e.0,1,2 (e / exploit-01~e.3
:ARG0 w2
:ARG1 (t / threshold~e.6
:poss~e.7 (s2 / small-molecule
:name (n / name :op1 "selumetinib"~e.8))
:mod (a3 / apoptosis~e.5))))
# ::id a_pmid_2234_3622.64 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The effects of selumetinib in combination with a number of key standard of care agents were tested pre @-@ clinically in human tumour xenograft models and resulted in enhanced anti @-@ tumour activity .
# ::alignments 1-1.1.1 2-1.1.1.1.r 3-1.1.1.1.1.1 4-1.1.1.2.r 5-1.1.1.2 6-1.1.1.2.1.r 8-1.1.1.2.1.2.2 9-1.1.1.2.1.2.2.r 10-1.1.1.2.1.1 11-1.1.1.2.1 13-1.1.1.2.1.2.1 14-1.1.1.2.1.2 16-1.1 19-1.1.2.1 20-1.1.3.r 21-1.1.3.2 22-1.1.3.1.1 23-1.1.3.1 24-1.1.3 25-1 26-1.2 27-1.2.2.r 28-1.2.2.1 29-1.2.2.2 31-1.2.2.2.1 32-1.2.2
(a / and~e.25
:op1 (t / test-01~e.16
:ARG1 (a2 / affect-01~e.1
:ARG0~e.2 (s / small-molecule
:name (n2 / name :op1 "selumetinib"~e.3))
:ARG1-of~e.4 (c / combine-01~e.5
:ARG2~e.6 (s2 / standard~e.11
:ARG1-of (k / key-02~e.10)
:mod (a4 / agent~e.14
:mod (c3 / care-03~e.13)
:quant~e.9 (n / number~e.8)))))
:time (b / before
:op1 (c2 / clinic~e.19))
:location~e.20 (m / model~e.24
:mod (x / xenograft~e.23
:mod (t2 / tumor~e.22))
:mod (h / human~e.21)))
:op2 (r / result-01~e.26
:ARG1 a2
:ARG2~e.27 (a3 / activity-06~e.32
:ARG1-of (e / enhance-01~e.28)
:ARG0-of (c4 / counter-01~e.29
:ARG1 t2~e.31))))
# ::id a_pmid_2234_3622.65 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok A number of compounds including the DNA @-@ alkylating agent TMZ and the anti @-@ mitotic drug docetaxel resulted in a greatly enhanced tumour growth inhibition compared with monotherapies ( Table 1 and supplementary Table 1 ) .
# ::alignments 1-1.1.2 2-1.1.2.r 3-1.1 4-1.1.1 6-1.1.1.1.1.1.1.2.1 9-1.1.1.1.1 10-1.1.1.1.1.2.1.1.1 11-1.1.1.1 13-1.1.1.1.2 13-1.1.1.1.2.2 13-1.1.1.1.2.2.r 15-1.1.1.1.2.2.1 17-1.1.1.1.2.1.1 18-1 19-1.2.r 21-1.2.2.1 22-1.2.2 23-1.2.1.1 24-1.2.1 25-1.2 26-1.2.2.2.r 31-1.3.1.1 31-1.3.1.2 32-1.3.1.1.1 32-1.3.1.2.1 34-1.3.1 36-1.3.1.2.2 37-1.3.1.1 37-1.3.1.2 38-1.3.1.1.1 38-1.3.1.2.1
(r / result-01~e.18
:ARG1 (c2 / compound~e.3
:ARG2-of (i3 / include-91~e.4
:ARG1 (a3 / and~e.11
:op1 (a4 / agent~e.9
:ARG0-of (a / alkylate-01
:ARG1 (n / nucleic-acid :wiki "DNA"
:name (n5 / name :op1 "DNA"~e.6)))
:ARG1-of (m3 / mean-01
:ARG2 (s3 / small-molecule
:name (n3 / name :op1 "TMZ"~e.10))))
:op2 (s2 / small-molecule~e.13
:name (n4 / name :op1 "docetaxel"~e.17)
:ARG0-of~e.13 (c3 / counter-01~e.13
:ARG1 (m2 / mitosis~e.15)))))
:quant~e.2 (n2 / number~e.1))
:ARG2~e.19 (i / inhibit-01~e.25
:ARG1 (g / grow-01~e.24
:ARG1 (t / tumor~e.23))
:ARG1-of (e / enhance-01~e.22
:ARG3 (g2 / great~e.21)
:compared-to~e.26 (m / monotherapy)))
:ARG1-of (d / describe-01
:ARG0 (a2 / and~e.34
:op1 (t2 / table~e.31,37 :mod 1~e.32,38)
:op2 (t3 / table~e.31,37 :mod 1~e.32,38
:ARG2-of (s / supplement-01~e.36)))))
# ::id a_pmid_2234_3622.66 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok However , combining selumetinib with gemcitabine did not enhance the anti @-@ tumour activity of the individual agents ( supplementary Table 1 ) .
# ::alignments 0-1 2-1.1.2 3-1.1.2.1.1.1 4-1.1.2.2.r 5-1.1.2.2.1.1 7-1.1.1 7-1.1.1.r 8-1.1 10-1.1.3.2 12-1.1.3.2.1 13-1.1.3 14-1.1.3.1.r 16-1.1.3.1.1 17-1.1.3.1 20-1.2.1.2 21-1.2.1 22-1.2.1.1
(c / contrast-01~e.0
:ARG2 (e / enhance-01~e.8 :polarity~e.7 -~e.7
:ARG0 (c2 / combine-01~e.2
:ARG1 (s2 / small-molecule
:name (n / name :op1 "selumetinib"~e.3))
:ARG2~e.4 (s3 / small-molecule
:name (n2 / name :op1 "gemcitabine"~e.5)))
:ARG1 (a / activity-06~e.13
:ARG0~e.14 (a2 / agent~e.17
:mod (i / individual~e.16))
:ARG0-of (c3 / counter-01~e.10
:ARG1 (t2 / tumor~e.12))))
:ARG1-of (d / describe-01
:ARG0 (t / table~e.21 :mod 1~e.22
:ARG2-of (s / supplement-01~e.20))))
# ::id a_pmid_2234_3622.67 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The data presented here suggests that when selumetinib is combined , with either TMZ or docetaxel , the resulting anti @-@ tumour phenotypes maybe due to mechanistic interactions between the two compounds .
# ::alignments 1-1.1 2-1.1.1 3-1.1.1.1 4-1 5-1.2.r 6-1.2.2.r 7-1.2.2.1.1.1 9-1.2.2 13-1.2.2.2.1.1.1 14-1.2.2.2 15-1.2.2.2.2.1.1 18-1.2.1.2.1 19-1.2.1.2.2 21-1.2.1.2.2.1 22-1.2.1.2 23-1.2 24-1.2.1 25-1.2.1 26-1.2.1.1.3 27-1.2.1.1
(s / suggest-01~e.4
:ARG0 (d / data~e.1
:ARG1-of (p2 / present-01~e.2
:medium (h / here~e.3)))
:ARG1~e.5 (p3 / possible-01~e.23
:ARG1 (c2 / cause-01~e.24,25
:ARG0 (i / interact-01~e.27
:ARG0 s2
:ARG1 o
:ARG2 (m / mechanistic~e.26))
:ARG1 (p / phenotype~e.22
:ARG2-of (r / result-01~e.18)
:ARG0-of (c3 / counter-01~e.19
:ARG1 (t2 / tumor~e.21))))
:time~e.6 (c / combine-01~e.9
:ARG1 (s2 / small-molecule
:name (n2 / name :op1 "selumetinib"~e.7))
:ARG2 (o / or~e.14
:op1 (s4 / small-molecule
:name (n3 / name :op1 "TMZ"~e.13))
:op2 (s3 / small-molecule
:name (n / name :op1 "docetaxel"~e.15))))))
# ::id a_pmid_2234_3622.68 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Selumetinib in combination with TMZ enhances DNA damage
# ::alignments 0-1.1.1.1.1 2-1.1 3-1.1.2.r 4-1.1.2.1.1 5-1 6-1.2.2.2.1 7-1.2
(e / enhance-01~e.5
:ARG0 (c / combine-01~e.2
:ARG1 (s / small-molecule
:name (n / name :op1 "selumetinib"~e.0))
:ARG2~e.3 (s2 / small-molecule
:name (n2 / name :op1 "TMZ"~e.4)))
:ARG1 (d / damage-01~e.7
:ARG0 c
:ARG1 (n3 / nucleic-acid :wiki "DNA"
:name (n4 / name :op1 "DNA"~e.6))))
# ::id a_pmid_2234_3622.69 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The combination of selumetinib and TMZ in the SW @-@ 620 human tumour xenograft model resulted in a significantly enhanced anti @-@ tumour efficacy ( 103.5 % inhibition ; P @ < 0.0005 ) , compared with selumetinib ( 52 % inhibition ; P @ < 0.0005 ) and TMZ ( 88 % inhibition ; P @ < 0.0005 ) alone ( Figure 2A ) .
# ::alignments 1-1.1 3-1.4.1.1.1 4-1.4 5-1.1.2 6-1.1.3.r 8-1.1.3.1.1 10-1.1.3.1.1 11-1.1.3.2.1.1 12-1.1.3.2.1 13-1.1.3.2 15-1 16-1.2.r 18-1.2.2.1 19-1.2.2 20-1.2.1 22-1.2.1.1 23-1.2 25-1.2.3.1.1.1.1 26-1.2.3.1.1.1 27-1.2.3.1.1 30-1.2.3.1.2 32-1.2.3.1.2.1 33-1.2.3.1.2.1.1 36-1.4.r 38-1.4.1.1.1 40-1.4.1.2.1.1 41-1.4.1.2.1 42-1.4.1 42-1.4.1.2 42-1.4.1.2.r 45-1.4.1.3 46-1.4.1.3 47-1.4.1.3 48-1.4.1.3 50-1.2.3.1 51-1.4.2.1.1 53-1.4.2.2.1.1 54-1.4.2.2.1 55-1.4.2 55-1.4.2.2 55-1.4.2.2.r 58-1.4.2.3 59-1.4.2.3 60-1.4.2.3 61-1.4.2.3 63-1.4.3 66-1.3.1 67-1.3.1.1
(r / result-01~e.15
:ARG1 (c2 / combine-01~e.1
:ARG1 s2
:ARG2 s3~e.5
:location~e.6 (c3 / cell-line
:name (n / name :op1 "SW-620"~e.8,10)
:mod (x / xenograft~e.13
:mod (t3 / tumor~e.12
:mod (h / human~e.11)))))
:ARG2~e.16 (e / efficacy~e.23
:ARG0-of (c / counter-01~e.20
:ARG1 t3~e.22)
:ARG1-of (e2 / enhance-01~e.19
:ARG1-of (s / significant-02~e.18))
:ARG1-of (m5 / mean-01
:ARG2 (a3 / and~e.50
:op1 (i3 / inhibit-01~e.27
:degree (p / percentage-entity~e.26 :value 103.5~e.25))
:op2 (s4 / statistical-test-91~e.30
:ARG2 (l / less-than~e.32 :op1 0.0005~e.33)))))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.66 :mod "2A"~e.67))
:compared-to~e.36 (a / and~e.4
:op1 (s2 / small-molecule~e.42
:name (n2 / name :op1 "selumetinib"~e.3,38)
:ARG0-of~e.42 (i / inhibit-01~e.42
:degree (p2 / percentage-entity~e.41 :value 52~e.40))
:mod s4~e.45,46,47,48)
:op2 (s3 / small-molecule~e.55
:name (n3 / name :op1 "TMZ"~e.51)
:ARG0-of~e.55 (i2 / inhibit-01~e.55
:degree (p3 / percentage-entity~e.54 :value 88~e.53))
:mod s4~e.58,59,60,61)
:mod (a2 / alone~e.63)))
# ::id a_pmid_2234_3622.70 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok At the end of the dosing period , the monotherapy and combination treatment groups were left to observe the growth rate following the cessation of dosing ( animals in the control group had to be killed due to tumour size ) .
# ::alignments 2-1.2 3-1.2.1.r 5-1.2.1.1 6-1.2.1 9-1.1.1.1.1 10-1.1 11-1.1.2.1.1 12-1.1.1.1 12-1.1.2.1 13-1.1.1 13-1.1.2 15-1 17-1.3 19-1.3.1.1 20-1.3.1 21-1.3.1.2 23-1.3.1.2.1 24-1.3.1.2.1.1.r 25-1.3.1.2.1.1 27-1.3.1.2.1.2.1.1.1 28-1.3.1.2.1.2.1.1.1.1.r 30-1.3.1.2.1.2.1.1.1.1.1 31-1.3.1.2.1.2.1.1.1.1 35-1.3.1.2.1.2.1.1 36-1.3.1.2.1.2.1.2 37-1.3.1.2.1.2.1.2 38-1.3.1.2.1.2.1.2.1.1 39-1.3.1.2.1.2.1.2.1
(l / leave-17~e.15
:ARG1 (a / and~e.10
:op1 (g / group~e.13
:ARG1-of (t / treat-04~e.12
:ARG2 (m / monotherapy~e.9)))
:op2 (g2 / group~e.13
:mod (t2 / treat-04~e.12
:ARG1-of (c / combine-01~e.11))))
:time (e / end-01~e.2
:ARG1~e.3 (p / period~e.6
:time-of (d / dose-01~e.5)))
:purpose (o / observe-01~e.17
:ARG1 (r / rate~e.20
:mod (g3 / grow-01~e.19)
:ARG1-of (f / follow-01~e.21
:ARG2 (c2 / cease-01~e.23
:ARG1~e.24 d~e.25
:ARG1-of (m2 / mean-01
:ARG2 (o2 / obligate-01
:ARG1 (k / kill-01~e.35
:ARG1 (a2 / animal~e.27
:part-of~e.28 (g4 / group~e.31
:mod (c4 / control~e.30))))
:ARG1-of (c3 / cause-01~e.36,37
:ARG0 (s / size~e.39
:poss (t3 / tumor~e.38))))))))))
# ::id a_pmid_2234_3622.71 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In the selumetinib and TMZ monotherapy @-@ treated groups , tumour growth progressed rapidly once compound treatment had been removed .
# ::alignments 2-1.4.1.1.1.1.1 3-1.4 4-1.4.2.1.1.1.1 5-1.4.1.1.1.2 7-1.4.1.1 7-1.4.2.1 8-1.4.1 8-1.4.2 10-1.1.1 11-1.1 12-1 13-1.2 13-1.2.r 15-1.3.1.1.1 16-1.3.1.1 19-1.3.1
(p / progress-01~e.12
:ARG1 (g / grow-01~e.11
:ARG1 (t / tumor~e.10))
:manner~e.13 (r / rapid~e.13)
:ARG1-of (c / cause-01
:ARG0 (r2 / remove-01~e.19
:ARG1 (t2 / treat-04~e.16
:ARG2 (c2 / compound~e.15))))
:location (a / and~e.3
:op1 (g2 / group~e.8
:ARG1-of (t3 / treat-04~e.7
:ARG2 (s / small-molecule
:name (n / name :op1 "selumetinib"~e.2)
:mod (m2 / monotherapy~e.5))))
:op2 (g3 / group~e.8
:ARG1-of (t4 / treat-04~e.7
:ARG2 (s2 / small-molecule
:name (n2 / name :op1 "TMZ"~e.4)
:mod m2)))))
# ::id a_pmid_2234_3622.72 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In contrast , the start of tumour growth in the combination group was delayed for approximately 24 days from the start of the experiment compared with 15 days in the TMZ alone group .
# ::alignments 1-1 4-1.1.1 5-1.1.1.1.r 6-1.1.1.1.1 7-1.1.1.1 8-1.1.1.1.2.r 10-1.1.1.1.2.1 11-1.1.1.1.2 11-1.1.3.2 13-1.1 13-1.1.3 14-1.1.2.r 15-1.1.2 16-1.1.2.1.1 17-1.1.2.1.2 18-1.1.4.r 20-1.1.4 21-1.1.4.1.r 23-1.1.4.1 24-1.1.3.r 25-1.1.3.1.r 26-1.1.3.1.1 27-1.1.3.1.2 28-1.1.3.2.1.r 30-1.1.3.2.1.1.1 31-1.1.3.2.1.2 32-1.1.1.1.2
(c / contrast-01~e.1
:ARG2 (d3 / delay-01~e.13
:ARG1 (s / start-01~e.4
:ARG1~e.5 (g / grow-01~e.7
:ARG1 (t3 / tumor~e.6)
:location~e.8 (g2 / group~e.11,32
:mod (c2 / combine-01~e.10))))
:ARG2~e.14 (a / approximately~e.15
:op1 (t / temporal-quantity :quant 24~e.16
:unit (d / day~e.17)))
:compared-to~e.24 (d4 / delay-01~e.13
:ARG2~e.25 (t2 / temporal-quantity :quant 15~e.26
:unit (d2 / day~e.27))
:location (g4 / group~e.11
:mod~e.28 (s5 / small-molecule
:name (n / name :op1 "TMZ"~e.30)
:mod (a2 / alone~e.31))))
:time~e.18 (s4 / start-01~e.20
:ARG1~e.21 (e / experiment-01~e.23))))
# ::id a_pmid_2234_3622.73 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In order to investigate potential mechanisms , to explain the enhanced combination effect with TMZ , we used the growth inhibition data generated from our anti @-@ tumour studies to guide our pharmacodynamic sampling times ( Figure 2A ) .
# ::alignments 0-1.5.r 1-1.5.r 2-1.5.r 3-1.5.1 4-1.5.1.2.1 5-1.5.1.2 8-1.5.2 10-1.5.2.2.2 11-1.5.2.2.1 12-1.5.2.2 13-1.5.2.2.1.1.r 14-1.5.2.2.1.1.1.1 16-1.5.2.1 17-1 17-1.5.r 19-1.2.1.1 20-1.2.1 21-1.2 22-1.2.2 24-1.2.2.1.1 24-1.2.2.1.1.r 25-1.3.1 26-1.3.1 27-1.3.1 28-1.3.1 30-1.3 31-1.3.2.1.1 31-1.3.2.1.1.r 32-1.3.2.1.2 33-1.3.2.1 34-1.3.2 34-1.3.2.1.r 37-1.4.1 38-1.4.1.1
(u / use-01~e.17
:ARG0 (w / we)
:ARG1 (d / data~e.21
:topic (i / inhibit-01~e.20
:ARG1 (g / grow-01~e.19))
:ARG1-of (g2 / generate-01~e.22
:ARG2 (s / study-01
:ARG0~e.24 w~e.24
:ARG0-of (c2 / counter-01
:ARG1 (t3 / tumor)))))
:ARG2 (g3 / guide-01~e.30
:ARG0 d~e.25,26,27,28
:ARG1 (t / time~e.34
:time-of~e.34 (s2 / sample-01~e.33
:ARG0~e.31 w~e.31
:mod (p / pharmacodynamic~e.32))))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.37 :mod "2A"~e.38))
:purpose~e.0,1,2,17 (a / and
:op1 (i2 / investigate-01~e.3
:ARG0 w
:ARG1 (m / mechanism~e.5
:mod (p2 / potential~e.4)))
:op2 (e / explain-01~e.8
:ARG0 w~e.16
:ARG1 (a2 / affect-01~e.12
:ARG0 (c / combine-01~e.11
:ARG2~e.13 (s3 / small-molecule
:name (n / name :op1 "TMZ"~e.14)))
:ARG1-of (e2 / enhance-01~e.10)))))
# ::id a_pmid_2234_3622.74 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Samples were collected at the end of the TMZ dosing ( PD1 ) , when the TMZ and combination groups growth rate started to diverge ( PD2 ) , at the end of selumetinib dosing ( PD3 ) and at the end of the re @-@ growth period ( PD4 ) ( Figure 2A ; white arrows on graph ) .
# ::alignments 0-1.1 0-1.1.1 0-1.1.1.r 2-1 5-1.3.1 8-1.3.1.1.1.1.1 9-1.3.1.1 11-1.3.1.2.1.1.1 14-1.3.r 16-1.3.1.1.1.1.1 17-1.3 18-1.3.2.1.2.1.1.1 19-1.3.2.1.1.1.1 19-1.3.2.1.2.1.1 20-1.3.2.1.1.1 20-1.3.2.1.2.1 21-1.3.2.1.1 21-1.3.2.1.2 22-1.3.2 24-1.3.2.1 26-1.3.2.2.1.1.1 31-1.3.1 31-1.3.3 33-1.3.3.1.1.1.1 34-1.3.3.1 36-1.3.3.2.1.1.1 38-1.3 41-1.3.1 41-1.3.3 41-1.3.4 46-1.3.4.1 49-1.3.4.2.1.1.1 53-1.2.1.1 54-1.2.1.1.1 57-1.2.1.2.1 58-1.2.1.2 59-1.2.1.2.2.r 60-1.2.1.2.2
(c / collect-01~e.2
:ARG1 (t5 / thing~e.0
:ARG1-of~e.0 (s / sample-01~e.0))
:ARG1-of (d2 / describe-01
:ARG0 (a / and
:op1 (f / figure~e.53 :mod "2A"~e.54)
:op2 (a2 / arrow~e.58
:ARG1-of (w / white-03~e.57)
:location~e.59 (g2 / graph~e.60))))
:time~e.14 (a6 / and~e.17,38
:op1 (e / end-01~e.5,31,41
:ARG1 (d / dose-01~e.9
:ARG2 (s4 / small-molecule
:name (n6 / name :op1 "TMZ"~e.8,16)))
:ARG1-of (l / label-01
:ARG2 (t2 / thing
:name (n / name :op1 "PD1"~e.11))))
:op2 (s2 / start-01~e.22
:ARG1 (d4 / diverge-01~e.24
:ARG0 (r / rate~e.21
:mod (g6 / grow-01~e.20
:ARG1 (g / group~e.19
:mod s4)))
:ARG1 (r2 / rate~e.21
:mod (g7 / grow-01~e.20
:ARG1 (g8 / group~e.19
:mod (c2 / combine-01~e.18)))))
:ARG1-of (l2 / label-01
:ARG2 (t3 / thing
:name (n4 / name :op1 "PD2"~e.26))))
:op3 (e2 / end-01~e.31,41
:ARG1 (d3 / dose-01~e.34
:ARG2 (s3 / small-molecule
:name (n5 / name :op1 "selumetinib"~e.33)))
:ARG1-of (l3 / label-01
:ARG2 (t4 / thing
:name (n3 / name :op1 "PD3"~e.36))))
:op4 (e3 / end-01~e.41
:ARG1 (g3 / grow-01~e.46
:mod (a4 / again))
:ARG1-of (l4 / label-01
:ARG2 (t / thing
:name (n2 / name :op1 "PD4"~e.49))))))
# ::id a_pmid_2234_3622.75 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok IHC analysis and histological scoring was performed on all the tissues collected to examine , selumetinib effects ( pERK1 @/@ 2 ) , DNA damage ( γ @ H2A.X ) , apoptosis ( cleaved caspase 3 ) and the cell cycle ( pHH3 ) ( scoring data not shown ) .
# ::alignments 1-1.1.1 2-1.1 3-1.1.2.1 4-1.1.2 6-1 7-1.2.r 8-1.2.1 10-1.2 11-1.2.2 12-1.2.2.1.r 13-1.2.2.1.1 13-1.2.2.1.2 13-1.2.2.1.3 13-1.2.2.1.4 15-1.2.2.1.1.1.1.1.1 16-1.2.2.1.1.1 20-1.2.2.1.1.1.2.1.1 23-1.2.2.1.2.1.1.2.1 24-1.2.2.1.2.1 32-1.2.2.1.3.1 34-1.2.2.1.3.2.1.1 35-1.2.2.1.3.2.1.2 36-1.2.2.1.3.2.1.3 38-1.2.2.1 40-1.2.2.1.4.1.1 41-1.2.2.1.4.1 46-1.3.2.1 47-1.3.2 48-1.3.1 48-1.3.1.r 49-1.3
(p / perform-02~e.6
:ARG1 (a5 / and~e.2
:op1 (a6 / analyze-01~e.1
:mod (i / immunohistochemistry))
:op2 (s2 / score-01~e.4
:ARG3 (h / histology~e.3)))
:location~e.7 (t / tissue~e.10
:mod (a7 / all~e.8)
:ARG1-of (c3 / collect-01~e.11
:purpose~e.12 (a4 / and~e.38
:op1 (e / examine-01~e.13
:ARG1 (a3 / affect-01~e.16
:ARG0 (s / small-molecule
:name (n5 / name :op1 "selumetinib"~e.15))
:ARG2 (e2 / enzyme
:name (n / name :op1 "ERK1/2"~e.20)
:ARG3-of (p2 / phosphorylate-01))))
:op2 (e3 / examine-01~e.13
:ARG1 (d / damage-01~e.24
:ARG1 (n7 / nucleic-acid :wiki "DNA"
:name (n8 / name :op1 "DNA"~e.23)))
:instrument (p5 / protein
:name (n2 / name :op1 "γH2A.X")))
:op3 (e4 / examine-01~e.13
:ARG1 (a2 / apoptosis~e.32)
:instrument (p6 / protein
:name (n3 / name :op1 "Cleaved"~e.34 :op2 "Caspase"~e.35 :op3 3~e.36)))
:op4 (e5 / examine-01~e.13
:ARG1 (c / cycle-02~e.41
:ARG1 (c2 / cell~e.40))
:instrument (p4 / protein
:name (n4 / name :op1 "HH3")
:ARG3-of (p3 / phosphorylate-01))))))
:ARG1-of (s3 / show-01~e.49 :polarity~e.48 -~e.48
:ARG0 (d3 / data~e.47
:mod (s4 / score-01~e.46))))
# ::id a_pmid_2234_3622.76 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The sampling timepoint , which gave us the greatest insight into the mechanistic effects of these agents was that taken when we started to see the TMZ and combination groups diverge ( PD2 ) .
# ::alignments 1-1.3.1 2-1 2-1.3 5-1.3.2 6-1.3.2.2 8-1.3.2.1.1 8-1.3.2.1.1.1 8-1.3.2.1.1.1.r 9-1.3.2.1 10-1.3.2.1.2.r 12-1.3.2.1.2.2 13-1.3.2.1.2 14-1.3.2.1.2.1.r 15-1.3.2.1.2.1.1 16-1.3.2.1.2.1 17-1.3.r 19-1.2 20-1.2.2.r 20-1.3.1.r 21-1.2.2.1 22-1.2.2 24-1.2.2.2 26-1.2.2.2.2.1.1.1.1 28-1.2.2.2.2.2.1 29-1.2.2.2.2.1 29-1.2.2.2.2.2 30-1.2.2.2.2 32-1.1.1.1
(t3 / timepoint~e.2
:mod (t5 / thing
:name (n / name :op1 "PD2"~e.32))
:ARG1-of (t4 / take-01~e.19
:ARG0 w
:time~e.20 (s3 / start-01~e.22
:ARG0 w~e.21
:ARG1 (s2 / see-01~e.24
:ARG0 w
:ARG1 (d / diverge-01~e.30
:ARG0 (g4 / group~e.29
:mod (s4 / small-molecule
:name (n2 / name :op1 "TMZ"~e.26)))
:ARG1 (g3 / group~e.29
:mod (c / combine-01~e.28)
:ARG1-of (m3 / mean-01))))))
:domain~e.17 (t / timepoint~e.2
:time-of~e.20 (s / sample-01~e.1)
:ARG0-of (g2 / give-01~e.5
:ARG1 (i / insight~e.9
:mod (g / great~e.8
:degree~e.8 (m / most~e.8))
:topic~e.10 (a / affect-01~e.13
:ARG0~e.14 (a2 / agent~e.16
:mod (t2 / this~e.15))
:mod (m2 / mechanistic~e.12)))
:ARG2 (w / we~e.6))))
# ::id a_pmid_2234_3622.77 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok As expected , in response to selumetinib or TMZ alone we saw changes in the mechanistic biomarkers pERK1 @/@ 2 ( decrease ) and γ @ H2A.X ( increase ) , respectively , and a reduction in mitotic cells as shown by pHH3 in the selumetinib group compared with an increase in the TMZ tissues ( Figure 2B ) .
# ::alignments 1-1.2.3 4-1 5-1.1.r 6-1.1.1.1.1 7-1.1 8-1.1.2.1.1 9-1.1.3 10-1.2.3.1 11-1.2 12-1.2.2.1 15-1.2.2.1.1.1 19-1.2.2.1.1.2.1.1.1.1 21-1.2.2.1.1.2.1.1 21-1.2.2.1.1.2.1.1.2 21-1.2.2.1.1.2.1.1.2.r 23-1.2.2 23-1.2.2.1.1.2.1 29-1.2.2.1.1.2.1.2 29-1.2.2.1.1.2.1.2.3 29-1.2.2.1.1.2.1.2.3.r 34-1.2.2 34-1.2.2.1.1.2.1 36-1.2.2.2 37-1.2.2.2.1.r 38-1.2.2.2.1.1 39-1.2.2.2.1 40-1.2.2.2.2.r 41-1.2.2.2.2 44-1.2.2.2.2.2.r 46-1.2.2.2.2.2.1 47-1.2.2.2.2.2 48-1.2.2.2.3.r 51-1.2.2.1.1.2.1.2 51-1.2.2.1.1.2.1.2.3 51-1.2.2.1.1.2.1.2.3.r 51-1.2.2.2.3 52-1.2.2.2.3.1.r 54-1.2.2.2.3.1.1 55-1.2.2.2.3.1
(r2 / respond-01~e.4
:ARG1~e.5 (o / or~e.7
:op1 (s2 / small-molecule
:name (n4 / name :op1 "selumetinib"~e.6))
:op2 (s4 / small-molecule
:name (n5 / name :op1 "TMZ"~e.8))
:mod (a / alone~e.9))
:ARG2 (s3 / see-01~e.11
:ARG0 w
:ARG1 (a3 / and~e.23,34
:op1 (c / change-01~e.12
:ARG1 (b2 / biomarker
:mod (m3 / mechanistic~e.15)
:ARG1-of (m5 / mean-01
:ARG2 (a4 / and~e.23,34
:op1 (e2 / enzyme~e.21
:name (n / name :op1 "ERK1/2"~e.19)
:ARG1-of~e.21 (d / decrease-01~e.21)
:ARG3-of p2)
:op2 (p3 / protein~e.29,51
:name (n2 / name :op1 "γH2A.X")
:mod m3
:ARG1-of~e.29,51 (i / increase-01~e.29,51))))))
:op2 (r / reduce-01~e.36
:ARG1~e.37 (c2 / cell~e.39
:mod (m4 / mitosis~e.38))
:ARG1-of~e.40 (s / show-01~e.41
:ARG0 (p / protein
:name (n3 / name :op1 "HH3")
:ARG3-of (p2 / phosphorylate-01))
:location~e.44 (g / group~e.47
:mod s2~e.46))
:compared-to~e.48 (i2 / increase-01~e.51
:ARG1~e.52 (t2 / tissue~e.55
:mod s4~e.54))))
:ARG1-of (e / expect-01~e.1
:ARG0 (w / we~e.10))))
# ::id a_pmid_2234_3622.78 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Level of the apoptotic marker , cleaved caspase 3 , was comparable in the combination group compared with the TMZ monotherapy ( Figure 2B ) .
# ::alignments 0-1.1.1 1-1.1.1.1.r 3-1.1.1.1.2 4-1.1.1.1 6-1.1.1.1.1.1 7-1.1.1.1.1.2 8-1.1.1.1.1.3 12-1.1.1.2.r 14-1.1.1.2.1 15-1.1.1.2 16-1.1 17-1.1.2.r 19-1.1.2.1.1.1 20-1.1.2 23-1.2.1 24-1.2.1.1
(p / possible-01
:ARG1 (c / compare-01~e.16
:ARG1 (l / level~e.0
:degree-of~e.1 (m / marker~e.4
:name (n / name :op1 "cleaved"~e.6 :op2 "caspase"~e.7 :op3 3~e.8)
:mod (a / apoptosis~e.3))
:location~e.12 (g / group~e.15
:mod (c2 / combine-01~e.14)))
:ARG2~e.17 (m2 / monotherapy~e.20
:mod (s / small-molecule
:name (n2 / name :op1 "TMZ"~e.19))))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.23 :mod "2B"~e.24)))
# ::id a_pmid_2234_3622.79 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok However , in the combination group we observed a greatly enhanced upregulation of γ @ H2A.X compared with the TMZ group alone , suggesting that when selumetinib and TMZ are combined DNA damage is enhanced ( Figure 2B ) .
# ::alignments 0-1 2-1.1.r 4-1.1.2.2.1 5-1.1.2.2 5-1.1.2.3.2 6-1.1.1 7-1.1 9-1.1.2.3.1 10-1.1.2.3 11-1.1.2 17-1.1.2.3.2.r 18-1.1.2.3.2.1.r 20-1.1.2.3.2.1.1.1 21-1.1.2.2 22-1.1.2.3.2.1.2 24-1.1.2.4 25-1.1.2.4.1.r 26-1.1.2.4.1.2.r 27-1.1.2.4.1.2.1.1.1 29-1.1.2.4.1.2.2 31-1.1.2.4.1.2 32-1.1.2.4.1.1.1.2.1 33-1.1.2.4.1.1 35-1.1.2.4.1 38-1.2.1 39-1.2.1.1
(c / contrast-01~e.0
:ARG2~e.2 (o / observe-01~e.7
:ARG0 (w / we~e.6)
:ARG1 (u / upregulate-01~e.11
:ARG1 (p / protein
:name (n / name :op1 "γH2A.X"))
:location (g / group~e.5,21
:mod (c2 / combine-01~e.4))
:ARG1-of (e / enhance-01~e.10
:ARG3 (g2 / great~e.9)
:compared-to~e.17 (g3 / group~e.5
:mod~e.18 (s3 / small-molecule
:name (n3 / name :op1 "TMZ"~e.20)
:mod (a2 / alone~e.22))))
:ARG0-of (s / suggest-01~e.24
:ARG1~e.25 (e2 / enhance-01~e.35
:ARG1 (d / damage-01~e.33
:ARG1 (n4 / nucleic-acid :wiki "DNA"
:name (n5 / name :op1 "DNA"~e.32)))
:time~e.26 (c3 / combine-01~e.31
:ARG1 (s2 / small-molecule
:name (n2 / name :op1 "selumetinib"~e.27))
:ARG2 s3~e.29)))))
:ARG1-of (d3 / describe-01
:ARG0 (f / figure~e.38 :mod "2B"~e.39)))
# ::id a_pmid_2234_3622.80 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Selumetinib is efficacious in combination with docetaxel when dosed concurrently or following docetaxel
# ::alignments 0-1.2.1.1 1-1.2.r 2-1 4-1.2 4-1.2.2 4-1.2.2.r 5-1.2.2.1.r 6-1.2.2.1.1.1 7-1.1.r 8-1.1.1 9-1.1.1.2 10-1.1 11-1.1.2 12-1.1.2.2
(e / efficacious~e.2
:time~e.7 (o / or~e.10
:op1 (d / dose-01~e.8
:ARG1 (a / and
:op1 s3
:op2 s2)
:ARG1-of (c2 / concurrent-02~e.9))
:op2 (f / follow-01~e.11
:ARG1 s3
:ARG2 s2~e.12))
:domain~e.1 (s3 / small-molecule~e.4
:name (n2 / name :op1 "selumetinib"~e.0)
:ARG1-of~e.4 (c / combine-01~e.4
:ARG2~e.5 (s2 / small-molecule
:name (n / name :op1 "docetaxel"~e.6)))))
# ::id a_pmid_2234_3622.81 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Continuous , concurrent combinations of selumetinib and docetaxel resulted in significant anti @-@ tumour effects in several models ( Table 1 and Figure 3A ) .
# ::alignments 0-1.1.4 2-1.1.3 3-1.1 4-1.1.1.r 5-1.1.1.1.1 7-1.1.2.1.1 8-1 9-1.2.r 10-1.2.3 11-1.2.1 13-1.2.1.1 14-1.2 15-1.2.2.r 16-1.2.2.1 17-1.2.2 20-1.3.1.1 21-1.3.1.1.1 23-1.3.1 25-1.3.1.2 26-1.3.1.2.1
(r / result-01~e.8
:ARG1 (c / combine-01~e.3
:ARG1~e.4 (s / small-molecule
:name (n / name :op1 "selumetinib"~e.5))
:ARG2 (s4 / small-molecule
:name (n2 / name :op1 "docetaxel"~e.7))
:ARG1-of (c2 / concurrent-02~e.2)
:ARG1-of (c3 / continue-01~e.0))
:ARG2~e.9 (a / affect-01~e.14
:ARG2 (c4 / counter-01~e.11
:ARG0 (t / tumor~e.13))
:location~e.15 (m / model~e.17
:quant (s2 / several~e.16))
:ARG1-of (s3 / significant-02~e.10))
:ARG1-of (d2 / describe-01
:ARG0 (a2 / and~e.23
:op1 (t2 / table~e.20 :mod 1~e.21)
:op2 (f / figure~e.25 :mod "3A"~e.26))))
# ::id a_pmid_2234_3622.82 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok However , we were interested to explore the effect of dose sequencing on the anti @-@ tumour efficacy of these two agents as administration of selumetinib and docetaxel as monotherapies results in distinct cell cycle phenotypes ; a G1 or mitotic arrest , respectively .
# ::alignments 0-1 2-1.1.2.1 4-1.1.2 6-1.1.2.2 8-1.1.2.2.2 9-1.1.2.2.2.1.r 10-1.1.2.2.2.1.1 11-1.1.2.2.2.1 12-1.1.2.2.2.2.r 14-1.1.2.2.2.2.1.4 16-1.1.2.2.2.2.1.4.1 17-1.1.2.2.2.2 19-1.1.2.2.2.2.1.2 20-1.1.2.2.2.2.1.1 21-1.1.2.2.2.2.1 22-1.1.1.2.2.1.2.1.r 23-1.1.1.1 24-1.1.1.1.1.r 25-1.1.1.1.1.1.1.1 26-1.1.1.1.1 27-1.1.1.1.1.2.1.1 28-1.1.1.2.2.1.1.1.r 28-1.1.1.2.2.1.2.1.r 30-1.1.1 32-1.1.1.2.1.2 33-1.1.1.2.1.1 34-1.1.1.2.1 35-1.1.1.2 38-1.1.1.2.2.1.1.1.1.1 40-1.1.1.2.2.1.2.1 41-1.1.1.2.2.1.1 41-1.1.1.2.2.1.2
(c / contrast-01~e.0
:ARG2 (c2 / cause-01
:ARG0 (r / result-01~e.30
:ARG1 (a3 / administer-01~e.23
:ARG1~e.24 (a4 / and~e.26
:op1 (s2 / small-molecule
:name (n2 / name :op1 "selumetinib"~e.25))
:op2 (s3 / small-molecule
:name (n3 / name :op1 "docetaxel"~e.27)))
:manner (m / monotherapy))
:ARG2 (p / phenotype~e.35
:mod (c4 / cycle-02~e.34
:ARG1 (c5 / cell~e.33)
:mod (d2 / distinct~e.32))
:ARG1-of (m5 / mean-01
:ARG2 (a5 / and
:op2 (a6 / arrest-02~e.41
:time~e.28 (e3 / event
:name (n / name :op1 "G1"~e.38)))
:op3 (a7 / arrest-02~e.41
:time~e.22,28 (m2 / mitosis~e.40))))))
:ARG1 (i / interest-01~e.4
:ARG1 (w / we~e.2)
:ARG2 (e / explore-01~e.6
:ARG0 w
:ARG1 (a / affect-01~e.8
:ARG0~e.9 (s / sequence-01~e.11
:ARG1 (d / dose-01~e.10))
:ARG1~e.12 (e2 / efficacy~e.17
:poss (a2 / agent~e.21 :quant 2~e.20
:mod (t2 / this~e.19)
:ARG1-of (m4 / mean-01
:ARG2 a4)
:ARG0-of (c3 / counter-01~e.14
:ARG1 (t / tumor~e.16)))))))))
# ::id a_pmid_2234_3622.83 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Two schedules were designed in which mice bearing HCT @-@ 116 CRC tumours were treated with either a single dose of docetaxel ( 15 mg kg @ –1 ) followed 24 h later by selumetinib ( 25 mg kg @ –1 per bid ) for 7 days ( schedule 1 ) or selumetinib was administered as above for 7 days followed 24 h later with docetaxel ( schedule 2 ) ( Figure 3B ) .
# ::alignments 0-1.1.1 1-1.1 3-1 6-1.2.1.1 7-1.2.1.1.1 8-1.2.1.1.1.1.1.1.1 10-1.2.1.1.1.1.1.1.1 11-1.2.1.1.1.1.1.2.1.1 12-1.2.1.1.1.1 14-1.2.1 18-1.2.1.2.2.1 19-1.2.1.2 19-1.2.1.2.2 19-1.2.1.2.2.r 19-1.2.1.2.3.1 21-1.2.1.2.1.1 23-1.2.1.2.4.1 24-1.2.1.2.4.2 25-1.2.1.2.4.2 30-1.2.1.2.3 31-1.2.1.2.3.2.1.1 32-1.2.1.2.3.2.1.2 33-1.2.1.2.3.2 33-1.2.1.2.3.2.2 33-1.2.1.2.3.2.2.r 34-1.2.1.2.3.1.1.r 35-1.2.1.2.3.1.1.1.1 37-1.2.1.2.3.1.1.2.1 38-1.2.1.2.3.1.1.2.2 39-1.2.1.2.3.1.1.2.2 43-1.2.1.2.3.1.3 43-1.2.1.2.4.2 46-1.2.1.2.3.1.2.r 47-1.2.1.2.3.1.2.1 48-1.2.1.2.3.1.2.2 50-1.1 51-1.2.1.2.3.1.3.2.1 53-1.2 54-1.2.2.1 56-1.2.2 56-1.2.2.3.1 57-1.2.1.2.3.2.r 57-1.2.2.3.2.r 59-1.2.2.2.r 60-1.2.2.2 61-1.2.2.2 62-1.2.2.3 63-1.2.2.3.2 64-1.2.2.3.2 65-1.2.2.3.2 66-1.2.2.4 67-1.2.2.4 69-1.1 70-1.2.1.2.3.1.3.1 74-1.3.1 75-1.3.1.1
(d2 / design-01~e.3
:ARG1 (s / schedule~e.1,50,69 :quant 2~e.0)
:ARG3 (o / or~e.53
:op1 (t2 / treat-04~e.14
:ARG1 (m2 / mouse~e.6
:ARG0-of (b / bear-01~e.7
:ARG1 (t3 / tumor~e.12
:mod (c / cell-line
:name (n / name :op1 "HCT-116"~e.8,10)
:mod (d4 / disease
:name (n4 / name :op1 "CRC"~e.11))))))
:ARG2 (s5 / small-molecule~e.19
:name (n3 / name :op1 "docetaxel"~e.21)
:ARG2-of~e.19 (d5 / dose-01~e.19
:ARG1-of (s2 / single-02~e.18))
:ARG2-of (f2 / follow-01~e.30
:ARG1 (d6 / dose-01~e.19
:ARG2~e.34 (s3 / small-molecule
:name (n2 / name :op1 "selumetinib"~e.35)
:quant (c3 / concentration-quantity :quant 25~e.37
:unit m3~e.38,39))
:duration~e.46 (t / temporal-quantity :quant 7~e.47
:unit (d / day~e.48))
:frequency (r / rate-entity-91~e.43 :ARG1 2~e.70
:ARG2 (t5 / temporal-quantity :quant 1~e.51
:unit d)))
:time~e.57 (l / late~e.33
:op1 (t4 / temporal-quantity :quant 24~e.31
:unit (h / hour~e.32))
:degree~e.33 (m / more~e.33)))
:quant (c2 / concentration-quantity :quant 15~e.23
:unit (m3 / milligram-per-kilogram~e.24,25,43))))
:op2 (a / administer-01~e.56
:ARG1 s3~e.54
:duration~e.59 t~e.60,61
:ARG2-of (f3 / follow-01~e.62
:ARG1 (a3 / administer-01~e.56
:ARG1 s5)
:time~e.57 l~e.63,64,65)
:mod t2~e.66,67))
:ARG1-of (d3 / describe-01
:ARG0 (f / figure~e.74 :mod "3B"~e.75)))
# ::id a_pmid_2234_3622.84 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok As monotherapies , docetaxel and selumetinib resulted in 77 % ( P @ < 0.0005 ) and 50 % ( P @ < 0.005 ) tumour growth inhibition , respectively ( Figure 3C ) .
# ::alignments 3-1.1.1.1.1 4-1.1 5-1.1.2.1.1 6-1 7-1.2.r 8-1.2.1.1.2.1 9-1.2.1.1.2 12-1.2.1.2 14-1.2.1.2.1 15-1.2.1.2.1.1 17-1.2 18-1.2.2.1.2.1 19-1.2.2.1.2 22-1.2.2.2 24-1.2.2.2.1 25-1.2.2.2.1.1 27-1.2.1.1.1 28-1.2.1.1 28-1.2.2.1 29-1.2.1 29-1.2.2 34-1.3.1 35-1.3.1.1
(r / result-01~e.6
:ARG1 (a / and~e.4
:op1 (s2 / small-molecule
:name (n2 / name :op1 "docetaxel"~e.3))
:op2 (s / small-molecule
:name (n / name :op1 "selumetinib"~e.5))
:mod (m / monotherapy))
:ARG2~e.7 (a2 / and~e.17
:op1 (i / inhibit-01~e.29
:ARG1 (g / grow-01~e.28
:ARG1 (t / tumor~e.27)
:mod (p / percentage-entity~e.9 :value 77~e.8))
:ARG1-of (s3 / statistical-test-91~e.12
:ARG2 (l / less-than~e.14 :op1 0.0005~e.15)))
:op2 (i2 / inhibit-01~e.29
:ARG1 (g2 / grow-01~e.28
:ARG1 t
:mod (p2 / percentage-entity~e.19 :value 50~e.18))
:ARG1-of (s4 / statistical-test-91~e.22
:ARG2 (l2 / less-than~e.24 :op1 0.005~e.25))))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.34 :mod "3C"~e.35)))
# ::id a_pmid_2234_3622.85 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Interestingly , in the two combination schedules docetaxel administered before selumetinib ( schedule 1 ) resulted in a 110 % ( P @ < 0.0005 ) compared with 61 % ( P @ < 0.005 ) tumour growth inhibition when docetaxel was administered after selumetinib ( schedule 2 ) .
# ::alignments 0-1.3 4-1.4.1 5-1.4.2 6-1.4 7-1.1.1.1.1 8-1.1 8-1.1.2.1 9-1.1.2 10-1.1.2.1.1.1.1 12-1.1.2.2.1 13-1.1.2.2.1.1 15-1 16-1.2.r 18-1.2.1.1 19-1.2.1 22-1.2.3 24-1.2.3.1 25-1.2.3.1.1 27-1.2.2.r 29-1.2.2.2.1 30-1.2.2.2 33-1.2.3 35-1.2.3.1 38-1.2.2.1.1 39-1.2.2.1 40-1.2 40-1.2.2 41-1.1.2.r 41-1.2.2.3.r 42-1.2.2.3.1 44-1.2.2.3 45-1.2.2.3.2 46-1.2.2.3.2.1 48-1.2.2.3.3.1 48-1.4 49-1.2.2.3.3.1.1
(r / result-01~e.15
:ARG1 (a / administer-01~e.8
:ARG1 (s5 / small-molecule
:name (n / name :op1 "docetaxel"~e.7))
:time~e.41 (b / before~e.9
:op1 (a2 / administer-01~e.8
:ARG1 (s / small-molecule
:name (n2 / name :op1 "selumetinib"~e.10)))
:ARG1-of (m / mean-01
:ARG2 (s3 / schedule~e.12 :mod 1~e.13))))
:ARG2~e.16 (i3 / inhibit-01~e.40
:degree (p / percentage-entity~e.19 :value 110~e.18)
:compared-to~e.27 (i / inhibit-01~e.40
:ARG1 (g / grow-01~e.39
:ARG1 (t / tumor~e.38))
:degree (p2 / percentage-entity~e.30 :value 61~e.29)
:time~e.41 (a3 / administer-01~e.44
:ARG1 s5~e.42
:time (a4 / after~e.45
:op1 s~e.46)
:ARG1-of (m4 / mean-01
:ARG2 (s4 / schedule~e.48 :mod 2~e.49))))
:ARG1-of (s6 / statistical-test-91~e.22,33
:ARG2 (l2 / less-than~e.24,35 :op1 0.0005~e.25)))
:ARG0-of (i2 / interest-01~e.0)
:condition (s2 / schedule~e.6,48 :quant 2~e.4
:mod (c / combine-01~e.5)))
# ::id a_pmid_2234_3622.86 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok These results suggest that selumetinib could enhance the efficacy of docetaxel when administered in the sequence of docetaxel followed by selumetinib .
# ::alignments 0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 2-1 3-1.2.r 4-1.2.1.1.1.1 5-1.2 6-1.2.1 8-1.2.1.2 9-1.2.1.2.1.r 10-1.2.1.2.1.1.1 12-1.2.1.3 13-1.2.1.3.1.r 15-1.2.1.3.1 16-1.2.1.3.1.2.r 17-1.2.1.3.1.2.2 18-1.2.1.3.1.2 19-1.2.1.3.1.2.1.r 20-1.2.1.3.1.2.1
(s / suggest-01~e.2
:ARG0 (t / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1)
:mod (t2 / this~e.0))
:ARG1~e.3 (p / possible-01~e.5
:ARG1 (e / enhance-01~e.6
:ARG0 (s3 / small-molecule
:name (n2 / name :op1 "selumetinib"~e.4))
:ARG1 (e2 / efficacy~e.8
:poss~e.9 (s4 / small-molecule
:name (n / name :op1 "docetaxel"~e.10)))
:condition (a / administrate-01~e.12
:manner~e.13 (s2 / sequence~e.15
:poss s4
:mod~e.16 (f / follow-01~e.18
:ARG1~e.19 s3~e.20
:ARG2 s4~e.17))))))
# ::id a_pmid_2234_3622.87 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The sequence dependency of selumetinib when combined with docetaxel enhances apoptotic cell death
# ::alignments 1-1.1.2 2-1.1 3-1.1.1.r 4-1.1.1.1.1 6-1.1.1.2 7-1.1.1.2.1.r 8-1.1.1.2.1.1.1 9-1 10-1.2.2 11-1.2.1 12-1.2
(e / enhance-01~e.9
:ARG0 (d / depend-01~e.2
:ARG0~e.3 (s2 / small-molecule
:name (n / name :op1 "selumetinib"~e.4)
:ARG1-of (c / combine-01~e.6
:ARG2~e.7 (s3 / small-molecule
:name (n2 / name :op1 "docetaxel"~e.8))))
:ARG1 (s / sequence~e.1))
:ARG1 (d2 / die-01~e.12
:ARG1 (c2 / cell~e.11)
:mod (a / apoptosis~e.10)))
# ::id a_pmid_2234_3622.88 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In order to determine the mechanism of action in the scheduling studies with docetaxel , a series of tumour tissue samples were taken at different time points following exposure to the two dosing regimens ( Figure 4Ai and Bi ) .
# ::alignments 0-1.6.r 1-1.6.r 2-1.6.r 3-1.6 5-1.6.1 6-1.6.1.1.r 7-1.6.1.1 8-1.6.1.2.r 10-1.6.1.2.2 11-1.6.1.2 12-1.6.1.2.1.r 13-1.6.1.2.1.1.1 16-1.5 17-1.5.r 18-1.1.1 19-1.1 20-1 22-1.6.1.1 23-1.2.r 24-1.2.2 25-1.2.1 26-1.2 27-1.3 28-1.3.1 29-1.3.1.1.r 31-1.3.1.1.1 32-1.3.1.1.2 33-1.3.1.1 36-1.4.1.1 36-1.4.1.2 37-1.4.1.1.1 38-1.4.1
(s / sample-01~e.20
:ARG1 (t2 / tissue~e.19
:mod (t3 / tumor~e.18))
:time~e.23 (p / point~e.26
:mod (t / time~e.25)
:ARG1-of (d4 / differ-02~e.24))
:ARG1-of (f / follow-01~e.27
:ARG2 (e / expose-01~e.28
:ARG2~e.29 (r2 / regimen~e.33 :quant 2~e.31
:ARG0-of (d / dose-01~e.32))))
:ARG1-of (d2 / describe-01
:ARG0 (a / and~e.38
:op1 (f2 / figure~e.36 :mod "4Ai"~e.37)
:op2 (f3 / figure~e.36 :mod "4Bi")))
:quant~e.17 (s2 / series~e.16)
:purpose~e.0,1,2 (d3 / determine-01~e.3
:ARG1 (m / mechanism~e.5
:mod~e.6 (a2 / act-02~e.7,22)
:purpose~e.8 (s3 / study-01~e.11
:ARG1~e.12 (s5 / small-molecule
:name (n / name :op1 "docetaxel"~e.13))
:ARG1-of (s4 / schedule-01~e.10)))))
# ::id a_pmid_2234_3622.89 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To assess the cell cycle mechanistic effects the mitotic marker pHH3 was quantitated .
# ::alignments 1-1.2 3-1.2.1.1.1 4-1.2.1.1 5-1.2.1.2 6-1.2.1 8-1.1.1 9-1.1
(q / quantitate-01
:ARG1 (m / marker~e.9
:mod (m2 / mitosis~e.8)
:ARG1-of (m4 / mean-01
:ARG2 (p / protein
:name (n / name :op1 "HH3")
:ARG1-of (p2 / phosphorylate-01))))
:purpose (a / assess-01~e.1
:ARG1 (a2 / affect-01~e.6
:ARG1 (c / cycle-02~e.4
:ARG1 (c2 / cell~e.3))
:mod (m3 / mechanistic~e.5))))
# ::id a_pmid_2234_3622.90 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In the sequence when docetaxel was administered before selumetinib , increased levels of pHH3 were observed at the early timepoints ( PD1 & PD2 ) ( 2.7 @- and 2.3 @-@ fold change , respectively ; P @ < 0.0005 ) .
# ::alignments 2-1.3 4-1.3.1.1.1.1 6-1.3.1 6-1.3.1.2.1 7-1.3.1.2 8-1.3.1.2.1.1.1.1 10-1.1.1 11-1.1 12-1.5.1.1.1 15-1 18-1.2.1 21-1.4.1.1.1.1 22-1.4.1 23-1.4.1.2.1.1 26-1.5.1.1.1.1 28-1.5.1 29-1.5.1.2.1.1 31-1.5.1.1.1 31-1.5.1.2.1 32-1.5.1.1 32-1.5.1.2 37-1.1.1.1 37-1.1.2.2 39-1.1.1.1.1 40-1.1.1.1.1.1
(o / observe-01~e.15
:ARG1 (l / level~e.11
:ARG1-of (i / increase-01~e.10
:ARG1-of (s4 / statistical-test-91~e.37
:ARG2 (l2 / less-than~e.39 :op1 0.0005~e.40)))
:quant-of (p4 / protein
:name (n / name :op1 "HH3")
:ARG3-of (p5 / phosphorylate-01~e.37)))
:time (t / timepoint
:mod (e / early~e.18))
:location (s / sequence~e.2
:mod (a / administer-01~e.6
:ARG1 (s3 / small-molecule
:name (n5 / name :op1 "docetaxel"~e.4))
:time (b2 / before~e.7
:op1 (a2 / administer-01~e.6
:ARG1 (s2 / small-molecule
:name (n4 / name :op1 "selumetinib"~e.8))))))
:ARG1-of (m2 / mean-01
:ARG2 (a3 / and~e.22
:op1 (t2 / thing
:name (n2 / name :op1 "PD1"~e.21))
:op2 (t3 / thing
:name (n3 / name :op1 "PD2"~e.23))))
:ARG1-of (m3 / mean-01
:ARG2 (a5 / and~e.28
:op1 (c / change-01~e.32
:ARG2 (p2 / product-of~e.12,31 :op1 2.7~e.26))
:op2 (c2 / change-01~e.32
:ARG2 (p3 / product-of~e.31 :op1 2.3~e.29)))))
# ::id a_pmid_2234_3622.91 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In schedule 2 , pHH3 levels were seen to increase following docetaxel ( PD7 ) ( 3.4 @-@ fold ; P @ < 0.0005 ) ( Figure 4Aii and 4Bii ) .
# ::alignments 1-1.3 2-1.3.1 5-1.1.1 7-1 9-1.1 10-1.1.3 11-1.1.3.1.1.1 13-1.4.1.1.1 16-1.1.2.1 18-1.1.2 21-1.1.1.1.2 21-1.1.4 23-1.1.4.1 24-1.1.4.1.1 28-1.2.1.1 28-1.2.1.2 29-1.2.1.1.1 30-1.2.1 31-1.2.1.2.1
(s / see-01~e.7
:ARG1 (i / increase-01~e.9
:ARG1 (l / level~e.5
:quant-of (p3 / protein
:name (n2 / name :op1 "HH3")
:ARG3-of (p4 / phosphorylate-01~e.21)))
:ARG2 (p / product-of~e.18 :op1 3.4~e.16)
:ARG1-of (f / follow-01~e.10
:ARG2 (s2 / small-molecule
:name (n3 / name :op1 "docetaxel"~e.11)))
:ARG1-of (s4 / statistical-test-91~e.21
:ARG2 (l2 / less-than~e.23 :op1 0.0005~e.24)))
:ARG1-of (d2 / describe-01
:ARG0 (a / and~e.30
:op1 (f2 / figure~e.28 :mod "4Aii"~e.29)
:op2 (f3 / figure~e.28 :mod "4Bii"~e.31)))
:condition (s3 / schedule~e.1 :mod 2~e.2)
:ARG1-of (m3 / mean-01
:ARG2 (t / thing
:name (n / name :op1 "PD7"~e.13))))
# ::id a_pmid_2234_3622.92 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok When selumetinib was administered alone levels of pHH3 decreased at several measurement points compared with controls ( PD2 P @ < 0.0005 ; PD4 P @ < 0.005 ; PD5 P @ < 0.0005 ; PD6 P @ < 0.0005 ) consistent with the inhibition of the MEK @/@ ERK pathway resulting in a G1/S arrest .
# ::alignments 0-1.2.r 1-1.2.1.1.1 3-1.2 4-1.2.1.2 5-1.1 8-1 9-1.3.r 10-1.3.1 11-1.3.2 12-1.3 13-1.4.r 15-1.4 17-1.3.3.1.1.1.1 19-1.1.1.2 19-1.6 21-1.6.1 22-1.6.1.1 24-1.3.3.1.2.1.1 26-1.1.1.2 26-1.6 28-1.6.1 31-1.3.3.1.3.1.1 33-1.1.1.2 33-1.6 35-1.6.1 36-1.6.1.1 38-1.3.3.1.4.1.1 40-1.1.1.2 40-1.6 42-1.6.1 43-1.6.1.1 45-1.5 46-1.5.1.r 48-1.5.1 49-1.5.1.1.r 51-1.5.1.1.1.1 53-1.5.1.1.1.1 54-1.5.1.1 55-1.5.1.2 56-1.5.1.2.1.r 58-1.5.1.2.1.1.1.1 59-1.5.1.2.1
(d / decrease-01~e.8
:ARG1 (l / level~e.5
:quant-of (p7 / protein
:name (n3 / name :op1 "HH3")
:ARG3-of (p8 / phosphorylate-01~e.19,26,33,40)))
:time~e.0 (a / administer-01~e.3
:ARG1 (s / small-molecule
:name (n8 / name :op1 "selumetinib"~e.1)
:mod (a3 / alone~e.4)))
:time~e.9 (p2 / point~e.12
:quant (s2 / several~e.10)
:mod (m3 / measure-01~e.11)
:ARG1-of (m4 / mean-01
:ARG2 (a4 / and
:op1 (t / thing
:name (n4 / name :op1 "PD2"~e.17))
:op2 (t2 / thing
:name (n5 / name :op1 "PD4"~e.24))
:op3 (t4 / thing
:name (n6 / name :op1 "PD5"~e.31))
:op4 (t5 / thing
:name (n7 / name :op1 "PD6"~e.38)))))
:compared-to~e.13 (c / control~e.15)
:ARG1-of (c2 / consistent-01~e.45
:ARG2~e.46 (i / inhibit-01~e.48
:ARG1~e.49 (p / pathway~e.54
:name (n / name :op1 "MEK/ERK"~e.51,53))
:ARG1-of (r / result-01~e.55
:ARG2~e.56 (a2 / arrest-02~e.59
:time (e / event
:name (n2 / name :op1 "G1/S"~e.58))))))
:ARG1-of (s3 / statistical-test-91~e.19,26,33,40
:ARG2 (l2 / less-than~e.21,28,35,42 :op1 0.0005~e.22,36,43)))
# ::id a_pmid_2234_3622.93 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Interestingly , in both sequences in the combination there is a reduction in pHH3 compared with the docetaxel alone group at that timepoint ( PD2 and PD7 ) ( 3.8 @- and 2.5 @-@ fold change , respectively ; P @ < 0.0005 ) .
# ::alignments 0-1.2 3-1.3.1 4-1.3 5-1.3.2.r 7-1.3.2 11-1 14-1.4.r 17-1.4.1.1.1 18-1.4.1.2 19-1.4 20-1.5.r 21-1.5.1 22-1.5 24-1.5.2.1.1.1.1 25-1.5.2.1 26-1.5.2.1.2.1.1 29-1.6.1.1.1.1 31-1.6.1 32-1.6.1.2.1.1 34-1.6.1.1.1 34-1.6.1.2.1 35-1.6.1.1 35-1.6.1.2 40-1.1.2 40-1.7 42-1.7.1 43-1.7.1.1
(r / reduce-01~e.11
:ARG1 (p4 / protein
:name (n / name :op1 "HH3")
:ARG3-of (p5 / phosphorylate-01~e.40))
:ARG0-of (i / interest-01~e.0)
:location (s / sequence~e.4
:mod (b / both~e.3)
:mod~e.5 (c / combine-01~e.7))
:compared-to~e.14 (g / group~e.19
:mod (s2 / small-molecule
:name (n4 / name :op1 "docetaxel"~e.17)
:mod (a / alone~e.18)))
:time~e.20 (t / timepoint~e.22
:mod (t2 / that~e.21)
:ARG1-of (m2 / mean-01
:ARG2 (a2 / and~e.25
:op1 (t3 / thing
:name (n2 / name :op1 "PD2"~e.24))
:op2 (t4 / thing
:name (n3 / name :op1 "PD7"~e.26)))))
:ARG1-of (m5 / mean-01
:ARG2 (a3 / and~e.31
:op1 (c2 / change-01~e.35
:ARG2 (p / product-of~e.34 :op1 3.8~e.29))
:op2 (c3 / change-01~e.35
:ARG2 (p2 / product-of~e.34 :op1 2.5~e.32))))
:ARG1-of (s3 / statistical-test-91~e.40
:ARG2 (l / less-than~e.42 :op1 0.0005~e.43)))
# ::id a_pmid_2234_3622.94 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Levels of the apoptotic marker cleaved caspase 3 , in tumour tissue taken from the docetaxel followed by selumetinib group , increased in this combination group ( 16.8 @-@ fold change from the control ; P @ < 0.0005 ) compared with the single agents alone ( 3.5 @- and 2.4 @-@ fold change for docetaxel and selumetinib , respectively ) ( Figure 4Aiii PD2 ) .
# ::alignments 0-1.1 1-1.1.1.r 3-1.1.1.2 4-1.1.1 5-1.1.1.1.1 6-1.1.1.1.2 7-1.1.1.1.3 9-1.1.1.3.r 10-1.1.1.3.1 11-1.1.1.3 12-1.1.1.3.2 13-1.1.1.3.1.r 13-1.1.1.3.2.1.r 15-1.1.1.3.2.1.1.1.1 16-1.1.1.3.2.1.2 18-1.1.1.3.2.1.2.1.1.1.1 19-1.1.1.3.2.1 19-1.1.1.3.2.1.2.1 21-1 25-1.1.1.3.2.1 27-1.2.1.2.1 29-1.2.1.2 30-1.2.1 31-1.1.1.3.1.r 31-1.2.1.1.r 33-1.2.1.1 36-1.6 38-1.6.1 39-1.6.1.1 41-1.3.r 44-1.3.1 45-1.3 46-1.3.2 48-1.3.3.1.1.2.1 50-1.3.3.1 51-1.3.3.1.2.2.1 53-1.3.3.1.1.2 53-1.3.3.1.2.2 54-1.3.3.1.1 54-1.3.3.1.2 55-1.5.r 56-1.5 57-1.5 58-1.5 64-1.4.1
(i / increase-01~e.21
:ARG1 (l / level~e.0
:quant-of~e.1 (m / marker~e.4
:name (n / name :op1 "cleaved"~e.5 :op2 "caspase"~e.6 :op3 3~e.7)
:mod (a3 / apoptosis~e.3)
:location~e.9 (t / tissue~e.11
:source~e.13,31 (t2 / tumor~e.10)
:ARG1-of (t3 / take-01~e.12
:ARG2~e.13 (g / group~e.19,25
:mod (s3 / small-molecule
:name (n2 / name :op1 "docetaxel"~e.15))
:ARG2-of (f2 / follow-01~e.16
:ARG1 (g2 / group~e.19
:mod (s2 / small-molecule
:name (n3 / name :op1 "selumetinib"~e.18)))))))))
:ARG4 (a4 / and
:op1 (c / change-01~e.30
:ARG1~e.31 (c2 / control~e.33)
:ARG2 (p2 / product-of~e.29 :op1 16.8~e.27)))
:compared-to~e.41 (a / agent~e.45
:ARG1-of (s / single-02~e.44)
:mod (a2 / alone~e.46)
:ARG1-of (m2 / mean-01
:ARG2 (a5 / and~e.50
:op1 (c3 / change-01~e.54
:ARG0 s3
:ARG2 (p3 / product-of~e.53 :op1 3.5~e.48))
:op2 (c4 / change-01~e.54
:ARG0 s2
:ARG2 (p4 / product-of~e.53 :op1 2.4~e.51)))))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.64 :mod "4AiiiPD2"))
:location~e.55 g~e.56,57,58
:ARG1-of (s4 / statistical-test-91~e.36
:ARG2 (l2 / less-than~e.38 :op1 0.0005~e.39)))
# ::id a_pmid_2234_3622.95 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In comparison , tumour tissue analysed in the same study after the chronic dosing schedule of selumetinib did not demonstrate an increase in cleaved caspase 3 levels in the combination group when compared with the single agents alone .
# ::alignments 1-1.1.4 3-1.1.2.1 4-1.1.2 5-1.1.2.2 6-1.1.2.2.1.r 8-1.1.2.2.1.1 9-1.1.2.2.1 10-1.1.2.2.1.2 12-1.1.2.2.1.2.1.1.2 13-1.1.2.2.1.2.1.1 14-1.1.2.2.1.2.1 15-1.1.2.2.1.2.1.1.1.r 16-1.1.2.2.1.2.1.1.1.1.1 17-1.1.2.2.1 18-1.1.1 18-1.1.1.r 19-1.1 21-1.1.3 22-1.1.3.1.r 23-1.1.3.1.2.1.1 24-1.1.3.1.2.1.2 25-1.1.3.1.2.1.3 26-1.1.3.1 27-1.1.3.1.1.r 29-1.1.3.1.1.1 30-1.1.3.1.1 31-1.1.4.r 32-1 32-1.1.4 33-1.1.4.1.r 35-1.1.4.1.1 36-1.1.4.1 37-1.1.4.2
(c / compare-01~e.32
:ARG1 (d / demonstrate-01~e.19 :polarity~e.18 -~e.18
:ARG0 (t / tissue~e.4
:source (t2 / tumor~e.3)
:ARG1-of (a3 / analyze-01~e.5
:ARG0~e.6 (s2 / study-01~e.9,17
:ARG1-of (s3 / same-01~e.8)
:time (a4 / after~e.10
:op1 (s4 / schedule-01~e.14
:ARG1 (d2 / dose-01~e.13
:ARG2~e.15 (s5 / small-molecule
:name (n2 / name :op1 "selumetinib"~e.16))
:mod (c4 / chronic~e.12)))))))
:ARG1 (i / increase-01~e.21
:ARG1~e.22 (l / level~e.26
:location~e.27 (g / group~e.30
:mod (c2 / combine-01~e.29))
:quant-of (p / protein
:name (n / name :op1 "cleaved"~e.23 :op2 "caspase"~e.24 :op3 3~e.25))))
:time~e.31 (c3 / compare-01~e.1,32
:ARG2~e.33 (a / agent~e.36
:ARG1-of (s / single-02~e.35))
:mod (a2 / alone~e.37))))
# ::id a_pmid_2234_3622.96 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok When selumetinib was dosed before docetaxel an increase in cleaved caspase 3 was not observed in the combination group at any of the sampling timepoints compared with at least one of the monotherapies ( Figure 4Biii ) .
# ::alignments 0-1.3.r 0-1.5.1.r 0-1.5.r 1-1.3.1.1.1 3-1.3 3-1.3.2.1 4-1.3.2 5-1.3.2.1.1.1.1 7-1.2 8-1.2.1.r 9-1.2.1.1.1 10-1.2.1.1.2 11-1.2.1.1.3 13-1.1 13-1.1.r 14-1 15-1.4.r 17-1.4.1 18-1.4 19-1.2.2.1 23-1.5.1 25-1.2.2.r 27-1.2.2.1 28-1.2.2.1 29-1.2.2.1.1 35-1.6.1 36-1.6.1.1
(o / observe-01~e.14 :polarity~e.13 -~e.13
:ARG1 (i / increase-01~e.7
:ARG1~e.8 (p / protein
:name (n / name :op1 "cleaved"~e.9 :op2 "caspase"~e.10 :op3 3~e.11))
:compared-to~e.25 (m2 / monotherapy
:quant (a / at-least~e.19,27,28 :op1 1~e.29)
:ARG1-of (i2 / include-91
:ARG2 (m3 / monotherapy))))
:time~e.0 (d / dose-01~e.3
:ARG2 (s / small-molecule
:name (n3 / name :op1 "selumetinib"~e.1))
:time (b / before~e.4
:op1 (d2 / dose-01~e.3
:ARG2 (s3 / small-molecule
:name (n2 / name :op1 "docetaxel"~e.5)))))
:location~e.15 (g / group~e.18
:mod (c / combine-01~e.17))
:time~e.0 (t / timepoint
:time-of~e.0 (s2 / sample-01~e.23))
:ARG1-of (d4 / describe-01
:ARG0 (f / figure~e.35 :mod "4Biii"~e.36)))
# ::id a_pmid_2234_3622.97 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Representative IHC images from PD2 highlights the increase in pHH3 following docetaxel exposure and the increase in cleaved caspase 3 in the docetaxel followed by selumetinib group ( Figure 4C ) .
# ::alignments 0-1.1.1 2-1.1 3-1.1.2.r 4-1.1.2.1.1 5-1 7-1.2.1 10-1.2.1.2 11-1.2.1.2.1.2.1.1 12-1.2.1.2.1 13-1.2 15-1.2.1 15-1.2.2 16-1.2.2.1.r 17-1.2.2.1.2 18-1.2.2.1.1.1 19-1.2.2.1.1.2 20-1.2.2.2.r 22-1.2.2.2.1.1.1 23-1.2.2.2.1.2 24-1.2.2.2.1.2.1.r 25-1.2.2.2.1.2.1.1.1 26-1.2.2.2 29-1.3.1 30-1.3.1.1
(h / highlight-01~e.5
:ARG0 (i / image~e.2
:ARG0-of (r / represent-01~e.0)
:source~e.3 (t2 / thing
:name (n7 / name :op1 "PD2"~e.4))
:mod (i4 / immunohistochemistry))
:ARG1 (a / and~e.13
:op1 (i2 / increase-01~e.7,15
:ARG1 (p / protein
:name (n2 / name :op1 "HH3")
:ARG3-of (p3 / phosphorylate-01))
:ARG1-of (f / follow-01~e.10
:ARG2 (e / expose-01~e.12
:ARG1 p
:ARG2 (s / small-molecule
:name (n3 / name :op1 "docetaxel"~e.11)))))
:op2 (i3 / increase-01~e.15
:ARG1~e.16 (p2 / protein
:name (n4 / name :op1 "caspase"~e.18 :op2 3~e.19)
:ARG1-of (c / cleave-01~e.17))
:location~e.20 (g / group~e.26
:mod (s2 / small-molecule
:name (n5 / name :op1 "docetaxel"~e.22)
:ARG2-of (f3 / follow-01~e.23
:ARG1~e.24 (s3 / small-molecule
:name (n6 / name :op1 "selumetinib"~e.25)))))))
:ARG1-of (d / describe-01
:ARG0 (f2 / figure~e.29 :mod "4C"~e.30)))
# ::id a_pmid_2234_3622.98 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The data presented here suggests that the combination efficacy effect seen when docetaxel was dosed before selumetinib was due to an increase in apoptosis .
# ::alignments 1-1.1 2-1.1.1 3-1.1.1.1 4-1 5-1.2.r 7-1.2.2.1.1 9-1.2.2 10-1.2.2.2 11-1.2.2.2.1.2.r 11-1.2.2.2.1.r 12-1.2.2.2.1.1.1.1 14-1.2.2.2.1 14-1.2.2.2.1.2.1 15-1.2.2.2.1.2 16-1.2.2.2.1.2.1.1.1.1 18-1.2 19-1.2 21-1.2.1 22-1.2.1.1.r 23-1.2.1.1
(s / suggest-01~e.4
:ARG0 (d / data~e.1
:ARG1-of (p / present-01~e.2
:location (h / here~e.3)))
:ARG1~e.5 (c / cause-01~e.18,19
:ARG0 (i / increase-01~e.21
:ARG1~e.22 (a / apoptosis~e.23))
:ARG1 (a2 / affect-01~e.9
:ARG0 (e / efficient-01
:ARG1 (c2 / combine-01~e.7))
:ARG1-of (s2 / see-01~e.10
:time~e.11 (d2 / dose-01~e.14
:ARG2 (s3 / small-molecule
:name (n / name :op1 "docetaxel"~e.12))
:time~e.11 (b / before~e.15
:op1 (d3 / dose-01~e.14
:ARG2 (s4 / small-molecule
:name (n2 / name :op1 "selumetinib"~e.16)))))))))
# ::id a_pmid_2234_3622.99 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Sequence scheduling of selumetinib and the Aurora B kinase inhibitor , barasertib ( AZD1152 ) , results in tumour regression and increased cell death
# ::alignments 0-1.1.2 1-1.1 2-1.1.1.r 3-1.1.1.1.1.1 4-1.1.1 6-1.1.1.2.2.1.1.1 7-1.1.1.2.2.1.1.2 8-1.1.1.2.2.1 9-1.1.1.2 9-1.1.1.2.2 9-1.1.1.2.2.r 11-1.1.1.2.1.1 16-1 17-1.2.r 18-1.2.1.1 20-1.2 21-1.2.2.2 22-1.2.2.1 23-1.2.2
(r / result-01~e.16
:ARG1 (s / schedule-01~e.1
:ARG1~e.2 (a2 / and~e.4
:op1 (s2 / small-molecule
:name (n / name :op1 "selumetinib"~e.3))
:op2 (s3 / small-molecule~e.9
:name (n2 / name :op1 "barasertib"~e.11)
:ARG0-of~e.9 (i2 / inhibit-01~e.9
:ARG1 (k / kinase~e.8
:name (n3 / name :op1 "Aurora"~e.6 :op2 "B"~e.7)))))
:manner (s4 / sequence~e.0))
:ARG2~e.17 (a / and~e.20
:op1 (r2 / regress-01
:ARG1 (t / tumor~e.18))
:op2 (d / die-01~e.23
:ARG1 (c / cell~e.22)
:ARG1-of (i / increase-01~e.21))))
# ::id a_pmid_2234_3622.100 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The dose @-@ scheduling effects of combining selumetinib and docetaxel lead us to investigate the sequence dependency of selumetinib combined with another mitotic targeting agent , the Aurora B kinase inhibitor , barasertib ( AZD1152 ) ( 16 ) .
# ::alignments 1-1.1.2.1 3-1.1.2 4-1.1 5-1.1.1.r 6-1.1.1 7-1.1.1.1.1.1 9-1.1.1.2.1.1 10-1 11-1.2 13-1.3 15-1.3.2.2 16-1.3.2 17-1.3.2.1.r 18-1.3.2.1.1.1 19-1.3.2.1.2 20-1.3.2.1.2.1.r 21-1.3.2.1.2.1.3 22-1.3.2.1.2.1.1.1 23-1.3.2.1.2.1.1 24-1.3.2.1.2.1 27-1.3.2.1.2.1.2.1.2.1.1.1 28-1.3.2.1.2.1.2.1.2.1.1.2 29-1.3.2.1.2.1.2.1.2.1 30-1.3.2.1.2.1.2.1 30-1.3.2.1.2.1.2.1.2 30-1.3.2.1.2.1.2.1.2.r 32-1.3.2.1.2.1.2.1.1.1 37-1.4.1.1.1
(l / lead-03~e.10
:ARG0 (a / affect-01~e.4
:ARG0~e.5 (c / combine-01~e.6
:ARG1 (s / small-molecule
:name (n / name :op1 "selumetinib"~e.7))
:ARG2 (s2 / small-molecule
:name (n2 / name :op1 "docetaxel"~e.9)))
:ARG1 (s6 / schedule-01~e.3
:ARG1 (d2 / dose-01~e.1)))
:ARG1 (w / we~e.11)
:ARG2 (i / investigate-01~e.13
:ARG0 w
:ARG1 (d / depend-01~e.16
:ARG0~e.17 (s3 / small-molecule
:name (n3 / name :op1 "selumetinib"~e.18)
:ARG1-of (c2 / combine-01~e.19
:ARG2~e.20 (a2 / agent~e.24
:ARG0-of (t / target-01~e.23
:ARG1 (m / mitosis~e.22))
:ARG1-of (m2 / mean-01
:ARG2 (s5 / small-molecule~e.30
:name (n5 / name :op1 "barasertib"~e.32)
:ARG0-of~e.30 (i3 / inhibit-01~e.30
:ARG1 (k / kinase~e.29
:name (n4 / name :op1 "Aurora"~e.27 :op2 "B"~e.28)))))
:mod (a3 / another~e.21))))
:ARG1 (s4 / sequence~e.15)))
:ARG1-of (d3 / describe-01
:ARG0 (p / publication
:ARG1-of (c3 / cite-01 :ARG2 16~e.37))))
# ::id a_pmid_2234_3622.101 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We designed two regimes in which barasertib was dosed at 150 mg kg @ –1 per qd for 2 consecutive days through a mini @-@ pump ( MP ) with a 24 h gap followed by selumetinib 25 mg kg @ –1 per bid for 14 consecutive days ( schedule 1 ) or the reverse of this schedule where barasertib was dosed following selumetinib treatment ( schedule 2 ) ( Figure 5A ) .
# ::alignments 0-1.1 1-1 2-1.2.1 3-1.2 6-1.2.2.1.1.1.2.1 6-1.2.2.2.1.1.1 8-1.2.2.1 10-1.2.2.1.1.1.1 10-1.2.2.1.1.1.3.1 11-1.2.2.1.1.1.3.3 12-1.2.2.1.1.1.3.3 16-1.2.2.1.1.1.3.2 16-1.2.2.1.1.1.3.3 19-1.2.2.1.2.1 20-1.2.2.1.2.2.1 21-1.2.2.1.2.2 24-1.2.2.1.3.1 26-1.2.2.1.3 30-1.2.2.1.3.r 32-1.2.2.1.1.1.3.2.1.1 32-1.2.2.1.4.1.1 33-1.2.2.1.1.1.3.2.1.2 34-1.2.2.1.4 35-1.2.2.1.5 37-1.2.2.1.5.1.1.1.1 38-1.2.2.1.5.1.1.2.1 39-1.2.2.1.5.1.1.2.3 40-1.2.2.1.5.1.1.2.3 44-1.2.2.1.5.1.1.2.2 44-1.2.2.1.5.1.1.2.3 47-1.2.2.1.5.1.2.1 48-1.2.2.1.5.1.2.2 49-1.2.2.1.5.1.2.2 51-1.2.2.1.6.1 52-1.2.2.1.6.1.1 54-1.2.2 56-1.2.2.2.5 59-1.2.2.2.5.1 61-1.2.2.2.1.1.1 63-1.2.2.1 63-1.2.2.1.5.1 63-1.2.2.2 64-1.2.2.2.2 65-1.2.2.2.2.1.1.1.1 66-1.2.2.2.2.1 68-1.2.2.2.4.1 69-1.2.2.2.4.1.1 73-1.2.2.2.3.1 74-1.2.2.2.3.1.1
(d7 / design-01~e.1
:ARG0 (w / we~e.0)
:ARG1 (r4 / regime~e.3 :quant 2~e.2
:consist-of (o / or~e.54
:op1 (d / dose-01~e.8,63
:ARG2 (a / and
:op1 (s / small-molecule :quant 150~e.10
:name (n / name :op1 "barasertib"~e.6)
:quant (c2 / concentration-quantity :quant 150~e.10
:ARG1-of (r / rate-entity-91~e.16
:ARG2 (t / temporal-quantity :quant 24~e.32
:unit (h / hour~e.33)))
:unit (m2 / milligram-per-kilogram~e.11,12,16))))
:duration (t2 / temporal-quantity :quant 2~e.19
:unit (d3 / day~e.21
:mod (c / consecutive~e.20)))
:instrument~e.30 (p / pump~e.26
:mod (m3 / mini~e.24))
:manner (g / gap~e.34
:duration (t3 / temporal-quantity :quant 24~e.32
:unit h))
:ARG2-of (f / follow-01~e.35
:ARG1 (d5 / dose-01~e.63
:ARG1 (s2 / small-molecule
:name (n2 / name :op1 "selumetinib"~e.37)
:quant (c3 / concentration-quantity :quant 25~e.38
:ARG1-of (r2 / rate-entity-91~e.44
:ARG2 (t4 / temporal-quantity :quant 12
:unit h))
:unit (m / milligram-per-kilogram~e.39,40,44)))
:duration (t5 / temporal-quantity :quant 14~e.47
:unit d3~e.48,49)))
:ARG1-of (m9 / mean-01
:ARG2 (s5 / schedule~e.51 :mod 1~e.52)))
:op2 (d6 / dose-01~e.63
:ARG1 (s3 / small-molecule
:name (n3 / name :op1 "barasertib"~e.6,61))
:ARG2-of (f2 / follow-01~e.64
:ARG1 (t6 / treat-03~e.66
:ARG3 (s4 / small-molecule
:name (n4 / name :op1 "selumetinib"~e.65))))
:ARG1-of (d8 / describe-01
:ARG0 (f3 / figure~e.73 :mod "5A"~e.74))
:ARG1-of (m10 / mean-01
:ARG2 (s6 / schedule~e.68 :mod 2~e.69))
:ARG1-of (r3 / reverse-01~e.56
:ARG2 d~e.59)))))
# ::id a_pmid_2234_3622.102 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The CaLu @-@ 6 NSCLC human tumour xenograft model was used in this study as previous experience with both agents allowed us to select appropriate dose levels in order to investigate these schedules ( Davies et al , 2007 ; Wilkinson et al , 2007 ) .
# ::alignments 1-1.1.1.1.1 3-1.1.1.1.1 4-1.1.1.2.2.1.1 5-1.1.1.2.1 6-1.1.1.2 7-1.1.1 8-1.1 10-1 11-1.2.r 12-1.2.2 13-1.2 13-1.2.1 13-1.2.1.r 14-1.3.1.1.3.r 15-1.3.1.1.3 16-1.3.1.1 17-1.3.1.1.2.r 18-1.3.1.1.2.1 19-1.3.1.1.2 20-1.3.1 21-1.3.1.2.1 23-1.3.1.2 24-1.3.1.2.2.1.1 25-1.3.1.2.2.1 26-1.3.1.2.2 30-1.3.1.2.3 31-1.3.1.2.3.2.1 32-1.3.1.2.3.2 35-1.4.1.1.1.1.1.1 37-1.4.1.1.1 38-1.4.1.1.1.2.1 41-1.4.1.2.2 45-1.4.1.2.1.1.1.1 47-1.4.1 47-1.4.1.1.1 47-1.4.1.2.1 48-1.4.1.1.1.2.1 51-1.4.1.1.2.1
(u / use-01~e.10
:ARG1 (m / model~e.8
:mod (x2 / xenograft~e.7
:name (n / name :op1 "CaLu-6"~e.1,3)
:mod (t / tumor~e.6
:mod (h / human~e.5)
:mod (d / disease
:name (n2 / name :op1 "NSCLC"~e.4)))))
:ARG2~e.11 (t2 / thing~e.13
:ARG1-of~e.13 (s / study-01~e.13)
:mod (t3 / this~e.12))
:ARG1-of (c2 / cause-01
:ARG0 (a / allow-01~e.20
:ARG0 (e / experience-01~e.16
:ARG0 w
:ARG1~e.17 (a2 / agent~e.19
:mod (b / both~e.18))
:time~e.14 (p7 / previous~e.15))
:ARG1 (s2 / select-01~e.23
:ARG0 (w / we~e.21)
:ARG1 (l / level~e.26
:quant-of (d2 / dose-01~e.25
:ARG1-of (a3 / appropriate-02~e.24)))
:ARG3 (i / investigate-01~e.30
:ARG0 w
:ARG1 (s3 / schedule~e.32
:mod t3~e.31)))))
:ARG1-of (d3 / describe-01
:ARG0 (a4 / and~e.47
:op1 (p / publication-91
:ARG0 (a5 / and~e.37,47
:op1 (p2 / person
:name (n3 / name :op1 "Davies"~e.35))
:op2 (p3 / person
:mod (o / other~e.38,48)))
:time (d4 / date-entity :year 2007~e.51))
:op2 (p4 / publication-91
:ARG0 (a6 / and~e.47
:op1 (p5 / person
:name (n4 / name :op1 "Wilkinson"~e.45))
:op2 p3)
:time d4~e.41))))
# ::id a_pmid_2234_3622.103 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Selumetinib and barasertib alone resulted in 57 % ( P @ < 0.005 ) and 95 % ( P @ < 0.0005 ) tumour growth inhibition compared with the vehicle @-@ treated controls at day 21 after the start of dosing .
# ::alignments 0-1.1.1.1.1 1-1 2-1.2.1.1.1 3-1.1.1.2 4-1.1 4-1.2 5-1.1.2.r 6-1.1.2.2.1 7-1.1.2.2 10-1.1.2.4 12-1.1.2.4.1 13-1.1.2.4.1.1 15-1 16-1.2.2.2.1 17-1.2.2.2 20-1.2.2.4 22-1.2.2.4.1 23-1.2.2.4.1.1 25-1.1.2.1.1 26-1.1.2.1 27-1.1.2 27-1.2.2 28-1.1.1.3 29-1.1.1.3.1.r 31-1.1.1.3.1.1.1 33-1.1.1.3.1.1 34-1.1.1.3.1 35-1.1.2.3.r 36-1.1.2.3.2.2 37-1.1.2.3.2.1 38-1.1.2.3 40-1.1.2.3.1 41-1.1.2.3.1.1.r 42-1.1.2.3.1.1
(a3 / and~e.1,15
:op1 (r / result-01~e.4
:ARG1 (s / small-molecule
:name (n / name :op1 "selumetinib"~e.0)
:mod (a / alone~e.3)
:ARG1-of (c / compare-01~e.28
:ARG2~e.29 (c3 / control~e.34
:ARG1-of (t2 / treat-04~e.33
:ARG2 (v / vehicle~e.31)))))
:ARG2~e.5 (i / inhibit-01~e.27
:ARG1 (g / grow-01~e.26
:ARG1 (t / tumor~e.25))
:quant (p / percentage-entity~e.7 :value 57~e.6)
:time~e.35 (a2 / after~e.38
:op1 (s2 / start-01~e.40
:ARG1~e.41 (d / dose-01~e.42))
:quant (t3 / temporal-quantity :quant 21~e.37
:unit (d2 / day~e.36)))
:ARG1-of (s4 / statistical-test-91~e.10
:ARG2 (l / less-than~e.12 :op1 0.005~e.13))))
:op2 (r2 / result-01~e.4
:ARG1 (s3 / small-molecule
:name (n2 / name :op1 "barasertib"~e.2)
:mod a
:ARG1-of c)
:ARG2 (i2 / inhibit-01~e.27
:ARG1 g
:quant (p2 / percentage-entity~e.17 :value 95~e.16)
:time a2
:ARG1-of (s5 / statistical-test-91~e.20
:ARG2 (l2 / less-than~e.22 :op1 0.0005~e.23)))))
# ::id a_pmid_2234_3622.104 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In comparison when selumetinib was dosed before barasertib the anti @-@ tumour efficacy was 74 % ( P @ < 0.0005 ) in contrast to 106 % ( P @ < 0.0005 ) observed when selumetinib was dosed following barasertib .
# ::alignments 1-1.4 2-1.1.2.r 3-1.1.1.1.1 5-1.1 5-1.1.2.1 6-1.1.2 7-1.1.2.1.1.1.1 9-1.2 11-1.2.1 14-1.5.1 15-1.5 18-1.6 20-1.6.1 21-1.6.1.1 24-1.3 26-1.3.1.1.1 27-1.3.1.1 30-1.3.1.3 30-1.6 32-1.6.1 33-1.6.1.1 35-1.3.1.2 36-1.3.1.2.1.r 37-1.3.1.2.1.1 39-1.3.1.2.1 40-1.3.1.2.1.2 41-1.3.1.2.1.2.1
(e3 / efficient-01
:ARG1 (d / dose-01~e.5
:ARG1 (s / small-molecule
:name (n / name :op1 "selumetinib"~e.3))
:time~e.2 (b / before~e.6
:op1 (d2 / dose-01~e.5
:ARG1 (s2 / small-molecule
:name (n2 / name :op1 "barasertib"~e.7)))))
:ARG2 (o / oppose-01~e.9
:ARG1 (t / tumor~e.11))
:ARG1-of (c / contrast-01~e.24
:ARG2 (e2 / efficient-01
:quant (p3 / percentage-entity~e.27 :value 106~e.26)
:ARG1-of (o2 / observe-01~e.35
:time~e.36 (d3 / dose-01~e.39
:ARG1 s~e.37
:ARG1-of (f / follow-01~e.40
:ARG2 s2~e.41)))
:ARG1-of (s4 / statistical-test-91~e.30
:ARG2 l)))
:ARG1-of (c2 / compare-01~e.1)
:quant (p / percentage-entity~e.15 :value 74~e.14)
:ARG1-of (s3 / statistical-test-91~e.18,30
:ARG2 (l / less-than~e.20,32 :op1 0.0005~e.21,33)))
# ::id a_pmid_2234_3622.105 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok At 21 days after the start of dosing the control , animals had to be culled due to tumour size ; however , the monotherapy and combination @-@ treated groups were kept on study for a further 14 days .
# ::alignments 1-1.1.1.3.2.1 2-1.1.1.3.2.2 3-1.1.1.3 5-1.1.1.3.1 6-1.1.1.3.1.1.r 7-1.1.1.3.1.1 9-1.1.1.3.1.1.1 11-1.1.1.1 13-1.1.1.2 15-1.1.1 16-1.1.1.2 17-1.1.1.2 18-1.1.1.2.1.1 19-1.1.1.2.1 21-1.2 24-1.2.1.1.1.1 25-1.2.1.1 26-1.2.1.1.2.1.1 28-1.2.1.1.2.1 29-1.2.1.1.1 29-1.2.1.1.2 31-1.2.1 32-1.2.1.1.r 33-1.2.1.1.3 34-1.2.1.2.r 36-1.2.1.2.2 37-1.2.1.2.1 38-1.2.1.2.3
(m / multi-sentence
:snt1 (o / obligate-01
:ARG2 (c / cull-01~e.15
:ARG1 (a / animal~e.11)
:ARG1-of (c2 / cause-01~e.13,16,17
:ARG0 (s / size-01~e.19
:ARG1 (t / tumor~e.18)))
:time (a2 / after~e.3
:op1 (s2 / start-01~e.5
:ARG1~e.6 (d / dose-01~e.7
:ARG1 (c3 / control~e.9)))
:quant (t2 / temporal-quantity :quant 21~e.1
:unit (d2 / day~e.2)))))
:snt2 (h / have-concession-91~e.21
:ARG2 (k / keep-01~e.31
:ARG1~e.32 (a3 / and~e.25
:op1 (g / group~e.29
:mod (m2 / monotherapy~e.24))
:op2 (g2 / group~e.29
:ARG1-of (t3 / treat-04~e.28
:ARG2 (c5 / combine-01~e.26)))
:ARG1-of (s3 / study-01~e.33))
:duration~e.34 (t5 / temporal-quantity :quant 14~e.37
:mod (f / further~e.36)
:unit d2~e.38))))
# ::id a_pmid_2234_3622.106 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok During this time , the tumours in the monotherapy and schedule 2 groups started to re @-@ grow .
# ::alignments 0-1.3.r 1-1.3.1 2-1.3 2-1.3.r 5-1.1 6-1.1.1.r 8-1.1.1.1.1 9-1.1.1 10-1.1.1.2.1 11-1.1.1.2.1.1 12-1.1.1.1 12-1.1.1.2 13-1 17-1.2
(s / start-01~e.13
:ARG0 (t / tumor~e.5
:source~e.6 (a / and~e.9
:op1 (g / group~e.12
:mod (m / monotherapy~e.8))
:op2 (g2 / group~e.12
:mod (s2 / schedule~e.10 :mod 2~e.11))))
:ARG1 (g3 / grow-01~e.17
:ARG1 t
:mod (a2 / again))
:time~e.0,2 (t3 / time~e.2
:mod (t4 / this~e.1)))
# ::id a_pmid_2234_3622.107 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Interestingly , the tumours in the group where barasertib was administered before selumetinib ( schedule 1 ) tumour re @-@ growth was delayed ( Figure 5B ) .
# ::alignments 0-1.2 3-1.1.1 6-1.1.1.1 8-1.1.1.1.1.1.1.1 10-1.1.1.1.1 10-1.1.1.1.1.2.1 11-1.1.1.1.1.2 12-1.1.1.1.1.2.1.1.1.1 14-1.1.1.1.1.3.1 15-1.1.1.1.1.3.1.1 17-1.1.1 20-1.1 22-1 25-1.3.1 26-1.3.1.1
(d / delay-01~e.22
:ARG1 (g / grow-01~e.20
:ARG1 (t / tumor~e.3,17
:source (g2 / group~e.6
:ARG2-of (a / administer-01~e.10
:ARG1 (s / small-molecule
:name (n / name :op1 "barasertib"~e.8))
:time (b / before~e.11
:op1 (a2 / administer-01~e.10
:ARG1 (s2 / small-molecule
:name (n2 / name :op1 "selumetinib"~e.12))))
:ARG2-of (m / mean-01
:ARG1 (s3 / schedule~e.14 :mod 1~e.15))))))
:mod (i / interesting~e.0)
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.25 :mod "5B"~e.26)))
# ::id a_pmid_2234_3622.108 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In order to investigate this further , we performed pharmacodynamic analysis on tumour tissue .
# ::alignments 0-1.3.r 1-1.3.r 2-1.3.r 3-1.3 4-1.3.2 5-1.3.3 7-1.1 8-1 9-1.2.3 10-1.2 11-1.2.2.r 12-1.2.2.1 13-1.2.2
(p / perform-02~e.8
:ARG0 (w / we~e.7)
:ARG1 (a / analyze-01~e.10
:ARG0 w
:ARG1~e.11 (t / tissue~e.13
:mod (t2 / tumor~e.12))
:mod (p2 / pharmacodynamic~e.9))
:purpose~e.0,1,2 (i / investigate-01~e.3
:ARG0 w
:ARG1 (t3 / this~e.4)
:degree (f / further~e.5)))
# ::id a_pmid_2234_3622.109 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In schedule 1 we analysed tumour tissue at 24 h after the end of the barasertib infusion ( PD1 ) and at the end of the selumetinib @-@ dosing period ( PD2 ) ( Figure 5A ) .
# ::alignments 1-1.5 2-1.5.1 3-1.1 4-1 5-1.2.1 6-1.2 8-1.3.2.1 9-1.3.2.2 10-1.3 10-1.6.1 10-1.6.2 12-1.3.1 12-1.6.1.1 12-1.6.2.1 15-1.3.1.1.1.1.1 15-1.6.1.1.1.1.1.1.1 16-1.3.1.1 16-1.6.1.1.1.1 18-1.6.1.1.1.1.2.1.1 23-1.6.1.1 24-1.6.2.1.1.r 26-1.6.2.1.1.1.1.1.1 28-1.6.2.1.1.1 29-1.6.1.1.1 29-1.6.2.1.1 31-1.6.2.1.1.2.1.1 35-1.4.1 36-1.4.1.1
(a / analyze-01~e.4
:ARG0 (w / we~e.3)
:ARG1 (t / tissue~e.6
:mod (t2 / tumor~e.5))
:time (a2 / after~e.10
:op1 (e / end-01~e.12
:ARG1 (i / infuse-01~e.16
:ARG1 (s / small-molecule
:name (n / name :op1 "barasertib"~e.15))))
:quant (t3 / temporal-quantity :quant 24~e.8
:unit (h / hour~e.9)))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.35 :mod "5A"~e.36))
:location (s3 / schedule~e.1 :mod 1~e.2)
:time (a5 / and
:op1 (a3 / after~e.10
:op1 (e3 / end-01~e.12,23
:ARG1 (p2 / period~e.29
:duration-of (i2 / infuse-01~e.16
:ARG2 (s4 / small-molecule
:name (n3 / name :op1 "barasertib"~e.15))
:ARG1-of (d3 / describe-01
:ARG2 (s5 / string-entity :value "PD1"~e.18))))))
:op2 (a4 / after~e.10
:op1 (e2 / end-01~e.12
:ARG1~e.24 (p / period~e.29
:duration-of (d / dose-01~e.28
:ARG2 (s2 / small-molecule
:name (n2 / name :op1 "selumetinib"~e.26)))
:ARG1-of (d4 / describe-01
:ARG2 (s6 / string-entity :value "PD2"~e.31)))))))
# ::id a_pmid_2234_3622.110 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In schedule 2 , tumours were harvested 24 h after the end of the barasertib infusion at the end of the study ( PD3 ) ( Figure 5A ) .
# ::alignments 1-1.3 2-1.3.1 4-1.1 6-1 7-1.2.3.1 8-1.2.3.2 9-1.2.1 9-1.2.2 11-1.2.1.1 11-1.2.2.1 14-1.2.1.1.1.1.1.1 15-1.2.1.1.1 18-1.2.1.1 19-1.2.2.1.1.r 21-1.2.2.1.1 21-1.2.2.1.1.1 21-1.2.2.1.1.1.r 23-1.5.1.1 27-1.4.1 28-1.4.1.1
(h / harvest-01~e.6
:ARG1 (t / tumor~e.4)
:time (a / and
:op1 (a2 / after~e.9
:op1 (e / end-01~e.11,18
:ARG1 (i / infuse-01~e.15
:ARG1 (s / small-molecule
:name (n / name :op1 "barasertib"~e.14)))))
:op2 (a3 / after~e.9
:op1 (e2 / end-01~e.11
:ARG1~e.19 (t2 / thing~e.21
:ARG1-of~e.21 (s2 / study-01~e.21))))
:quant (t3 / temporal-quantity :quant 24~e.7
:unit (h2 / hour~e.8)))
:location (s3 / schedule~e.1 :mod 2~e.2)
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.27 :mod "5A"~e.28))
:ARG1-of (d2 / describe-01
:ARG2 (s4 / string-entity :value "PD3"~e.23)))
# ::id a_pmid_2234_3622.111 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Using flow cytometry we assessed tissues for polyploidy and demonstrated that compared with the vehicle @-@ treated control group , barasertib @-@ treated tumours resulted in increased polyploidy ( 1.7 @-@ fold change ; P @ < 0.05 ) in the PD1 samples consistent with the mechanism of this agent ( Figure 5C ) ( Wilkinson et al , 2007 ) .
# ::alignments 0-1.3 1-1.3.2.1 2-1.3.2 3-1.1.1 4-1.1 5-1.1.2 6-1.1.3.r 7-1.1.3 8-1 8-1.5.1.1 9-1.2 10-1.2.2.r 11-1.2.2.1.2 12-1.2.2.1.2.1.r 14-1.2.2.1.2.1.2.1 16-1.2.2.1.2.1.2 17-1.2.2.1.2.1.1 18-1.2.2.1.2.1 20-1.2.2.1.1.1.1.1 22-1.2.2.1.1 23-1.2.2.1 24-1.2.2 25-1.2.2.2.r 26-1.2.2.2.1 27-1.2.2.2 29-1.2.2.2.1.1.1 31-1.2.2.2.1.1 32-1.2.2.2.1.2.1 35-1.2.2.2.1.5 37-1.2.2.2.1.5.1 38-1.2.2.2.1.5.1.1 40-1.2.2.2.1.3.r 42-1.2.2.2.1.3.1.1.1 43-1.2.2.2.1.3 44-1.2.2.2.1.4 45-1.2.2.2.1.4.1.r 47-1.2.2.2.1.4.1 48-1.2.2.2.1.4.1.1.r 49-1.2.2.2.1.4.1.1.1 50-1.2.2.2.1.4.1.1 53-1.4.1 54-1.4.1.1 59-1.5.1.1.1.1.1 61-1.5.1.1 62-1.5.1.1.2.1 65-1.5.1.2.1
(a / and~e.8
:op1 (a2 / assess-01~e.4
:ARG0 (w / we~e.3)
:ARG1 (t / tissue~e.5)
:ARG2~e.6 (p / polyploidy~e.7))
:op2 (d / demonstrate-01~e.9
:ARG0 w
:ARG1~e.10 (r / result-01~e.24
:ARG1 (t2 / tumor~e.23
:ARG1-of (t3 / treat-04~e.22
:ARG2 (s / small-molecule
:name (n / name :op1 "barasertib"~e.20)))
:ARG1-of (c3 / compare-01~e.11
:ARG2~e.12 (g / group~e.18
:ARG0-of (c4 / control-01~e.17)
:ARG1-of (t6 / treat-03~e.16
:ARG2 (v / vehicle~e.14)))))
:ARG2~e.25 (p2 / polyploidy~e.27
:ARG1-of (i / increase-01~e.26
:ARG2 (p3 / product-of~e.31 :op1 1.7~e.29)
:ARG2-of (m / mean-01
:ARG1 (c / change-01~e.32
:ARG1 p2))
:source~e.40 (s2 / sample-01~e.43
:ARG2 (t4 / thing
:name (n2 / name :op1 "PD1"~e.42)))
:ARG1-of (c2 / consistent-01~e.44
:ARG2~e.45 (m2 / mechanism~e.47
:poss~e.48 (a3 / agent~e.50
:mod (t5 / this~e.49))))
:ARG1-of (s3 / statistical-test-91~e.35
:ARG2 (l / less-than~e.37 :op1 0.05~e.38))))))
:ARG2-of (u / use-01~e.0
:ARG0 w
:ARG1 (c5 / cytometry~e.2
:mod (f / flow~e.1)))
:ARG1-of (d2 / describe-01
:ARG0 (f2 / figure~e.53 :mod "5C"~e.54))
:ARG1-of (d3 / describe-01
:ARG0 (p4 / publication-91
:ARG0 (a4 / and~e.8,61
:op1 (p5 / person
:name (n3 / name :op1 "Wilkinson"~e.59))
:op2 (p6 / person
:mod (o / other~e.62)))
:time (d4 / date-entity :year 2007~e.65))))
# ::id a_pmid_2234_3622.112 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In the same experiment , we monitored the population of sub G1 cells in these groups .
# ::alignments 2-1.4.1 3-1.4 5-1.1 6-1 8-1.2 9-1.2.1.r 10-1.2.1.1.1 11-1.2.1.1.2 12-1.2.1 13-1.3.r 14-1.3.1 15-1.3
(m / monitor-01~e.6
:ARG0 (w / we~e.5)
:ARG1 (p / population~e.8
:consist-of~e.9 (c / cell-line~e.12
:name (n / name :op1 "sub"~e.10 :op2 "G1"~e.11)))
:location~e.13 (g / group~e.15
:mod (t / this~e.14))
:medium (e / experiment-01~e.3
:ARG1-of (s / same-01~e.2)))
# ::id a_pmid_2234_3622.113 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok At the end of the dosing period in schedule 1 ( PD2 ) , there was a significant increase ( 3.5 @-@ fold change ; P @ < 0.0005 ) in the sub G1 population in the combination compared with the vehicle @-@ treated controls and selumetinib monotherapy ( Figure 5Cii ) .
# ::alignments 2-1.7.1 3-1.7.1.1.r 5-1.7.1.1.1 6-1.7.1.1 7-1.7.1.1.3.r 8-1.7.1.1.3 9-1.7.1.1.3.1 11-1.7.1.1.2.1.1 17-1.3 18-1 20-1.2.1 22-1.2 23-1.2.2 26-1.8 28-1.8.1 29-1.8.1.1 31-1.1.r 33-1.1.1.1.1 34-1.1.1.1.2 35-1.1 36-1.1.2.r 38-1.1.2 39-1.6 40-1.6.1.r 42-1.6.1.1.1.1 44-1.6.1.1.1 45-1.6.1.1 46-1.6.1 47-1.6.1.2.1.1.1 48-1.6.1.2 51-1.5.1 52-1.5.1.1
(i / increase-01~e.18
:ARG1~e.31 (p / population~e.35
:consist-of (c / cell-line
:name (n / name :op1 "sub"~e.33 :op2 "G1"~e.34))
:ARG1-of~e.36 (c3 / combine-01~e.38))
:ARG2 (p2 / product-of~e.22 :op1 3.5~e.20
:ARG2-of (c2 / change-01~e.23))
:ARG1-of (s / significant-02~e.17)
:ARG2-of (m / mean-01)
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.51 :mod "5Cii"~e.52))
:ARG1-of (c4 / compare-01~e.39
:ARG2~e.40 (a / and~e.46
:op1 (c5 / control~e.45
:ARG1-of (t / treat-04~e.44
:ARG2 (v / vehicle~e.42)))
:op2 (m2 / monotherapy~e.48
:mod (s2 / small-molecule
:name (n2 / name :op1 "selumetinib"~e.47)))))
:time (a2 / after
:op1 (e / end-01~e.2
:ARG1~e.3 (p4 / period~e.6
:duration-of (d2 / dose-01~e.5)
:ARG1-of (d3 / describe-01
:ARG2 (s5 / string-entity :value "PD2"~e.11))
:time~e.7 (s3 / schedule~e.8 :mod 1~e.9))))
:ARG1-of (s4 / statistical-test-91~e.26
:ARG2 (l / less-than~e.28 :op1 0.0005~e.29)))
# ::id a_pmid_2234_3622.114 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In comparison , the sub G1 populations in schedule 2 ( PD3 ) were increased ∼2 @-@ fold in both the monotherapy and combination groups ( Figure 5Dii ) .
# ::alignments 1-1.5 4-1.1.1.1.1 5-1.1.1.1.2 6-1.1 8-1.3 9-1.2.1.1 9-1.3.1 11-1.3.2.1.1 14-1 17-1.2.1 21-1.6.1.1 22-1.6 23-1.6.2.1 24-1.6.1 24-1.6.2 27-1.4.1 28-1.4.1.1
(i / increase-01~e.14
:ARG1 (p / population~e.6
:consist-of (c2 / cell-line
:name (n / name :op1 "sub"~e.4 :op2 "G1"~e.5)))
:ARG2 (a2 / approximately
:op1 (p2 / product-of~e.17 :op1 2~e.9))
:time (s / schedule~e.8 :mod 2~e.9
:ARG1-of (d2 / describe-01
:ARG2 (s2 / string-entity :value "PD3"~e.11)))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.27 :mod "5Dii"~e.28))
:ARG1-of (c / compare-01~e.1)
:location (a / and~e.22
:op1 (g / group~e.24
:mod (m / monotherapy~e.21))
:op2 (g2 / group~e.24
:ARG3-of (c3 / combine-01~e.23))))
# ::id a_pmid_2234_3622.115 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok These results suggest that the sustained anti @-@ tumour effect and regression observed when barasertib is scheduled before selumetinib is likely to be due to an avoidance of cell cycle @-@ mediated antagonism which allowed an increase in cell death .
# ::alignments 0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 2-1 3-1.2.r 5-1.2.1.2.1.2 6-1.2.1.2.1.1 8-1.2.1.2.1.1.1 9-1.2.1.2.1 10-1.2.1.2 12-1.2.1.2.3 13-1.2.1.2.3.1.r 14-1.2.1.2.3.1.1.1.1 16-1.2.1.2.3.1 16-1.2.1.2.3.1.2.1 17-1.2.1.2.3.1.2 18-1.2.1.2.3.1.2.1.1.1.1 20-1.2 21-1.2.1 23-1.2.1 24-1.2.1 26-1.2.1.1 28-1.2.1.1.1.1.1.1 29-1.2.1.1.1.1.1 31-1.2.1.1.1.1 34-1.2.1.1.1.2 36-1.2.1.1.1.2.1 37-1.2.1.1.1.2.1.1.r 38-1.2.1.1.1.2.1.1.1 39-1.2.1.1.1.2.1.1
(s / suggest-01~e.2
:ARG0 (t / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1)
:mod (t2 / this~e.0))
:ARG1~e.3 (l / likely-01~e.20
:ARG1 (c / cause-01~e.21,23,24
:ARG0 (a / avoid-01~e.26
:ARG1 (a2 / antagonize-02
:ARG1-of (m / mediate-01~e.31
:ARG0 (c2 / cycle-02~e.29
:ARG1 (c3 / cell~e.28)))
:ARG0-of (a3 / allow-01~e.34
:ARG1 (i / increase-01~e.36
:ARG1~e.37 (d / die-01~e.39
:ARG1 (c4 / cell~e.38))))))
:ARG1 (a4 / and~e.10
:op1 (a5 / affect-01~e.9
:ARG2 (o / oppose-01~e.6
:ARG1 (t3 / tumor~e.8))
:ARG1-of (s6 / sustain-01~e.5))
:op2 (r2 / regress-01)
:ARG1-of (o2 / observe-01~e.12
:time~e.13 (s2 / schedule-01~e.16
:ARG1 (s3 / small-molecule
:name (n / name :op1 "barasertib"~e.14))
:ARG3 (b / before~e.17
:op1 (s4 / schedule-01~e.16
:ARG1 (s5 / small-molecule
:name (n2 / name :op1 "selumetinib"~e.18))))))))))
# ::id bel_pmid_1002_9589.23800 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We present a model in which activation of the MAPK cascade signals via c @-@ fos/c @-@ jun family members to activate alpha 2 integrin gene expression .
# ::alignments 0-1.1 1-1 3-1.2 6-1.2.1.1 6-1.2.1.3 7-1.2.1.1.1.r 9-1.2.1.1.1.1.1 11-1.2.1 13-1.2.1.2.1.1.1.1.1 13-1.2.1.2.1.1.2.1.1 17-1.2.1.2.1.1.2.1.1 18-1.2.1.2.1.1.1 18-1.2.1.2.1.1.2 19-1.2.1.2 21-1.2.1.3 22-1.2.1.3.2.1.1.1 23-1.2.1.3.2.1.1.2 24-1.2.1.3.2.1.1.3 25-1.2.1.3.2.1 26-1.2.1.3.2
(p2 / present-01~e.1
:ARG0 (w / we~e.0)
:ARG1 (m / model~e.3
:location-of (s / signal-07~e.11
:ARG0 (a / activate-01~e.6
:ARG1~e.7 (p / pathway
:name (n / name :op1 "MAPK"~e.9)))
:instrument (m2 / member~e.19
:ARG1-of (i / include-91
:ARG2 (a2 / and
:op1 (p3 / protein-family~e.18
:name (n2 / name :op1 "c-fos"~e.13))
:op2 (p4 / protein-family~e.18
:name (n3 / name :op1 "c-jun"~e.13,17)))))
:purpose (a3 / activate-01~e.6,21
:ARG0 a
:ARG1 (e / express-03~e.26
:ARG1 (g / gene~e.25
:name (n4 / name :op1 "alpha"~e.22 :op2 2~e.23 :op3 "integrin"~e.24)))))))
# ::id bel_pmid_1002_9589.23888 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In addition , constitutive activation of the pathway via expression of the constitutively active mutants of MAPKK1 or MAPKK2 induced the expression of the platelet @/@ megakaryocytic @-@ specific genes alpha IIb and eta 3 .
# ::alignments 0-1.1.2.1 1-1.1.2.1 3-1.1.1.2 4-1.1.1 5-1.1.1.1.r 7-1.1.1.1 9-1.1.1.3 12-1.1.1.3.1.4.1 13-1.1.1.3.1.4 14-1.1.1.3.1.3 16-1.1.1.3.1.1.1.1 17-1.1.1.3.1 18-1.1.1.3.1.2.1.1 19-1.1 21-1.1.1.3 21-1.1.2 22-1.1.2.1.r 24-1.1.2.1.3.1.1.1 26-1.1.2.1.3.1.2.1.1 28-1.1.2.1.3 29-1.1.2.1.1 29-1.1.2.1.2 30-1.1.2.1.1.1.1 31-1.1.2.1.1.1.2 32-1 32-1.1.2.1
(a / and~e.32
:op2 (i / induce-01~e.19
:ARG0 (a2 / activate-01~e.4
:ARG1~e.5 (p / pathway~e.7)
:mod (c / constitutive~e.3)
:manner (e / express-03~e.9,21
:ARG2 (o / or~e.17
:op1 (e2 / enzyme
:name (n / name :op1 "MAPKK1"~e.16))
:op2 (e3 / enzyme
:name (n2 / name :op1 "MAPKK2"~e.18))
:ARG1-of (m2 / mutate-01~e.14)
:ARG0-of (a3 / activity-06~e.13
:mod c~e.12))))
:ARG2 (e4 / express-03~e.21
:ARG1~e.22 (a5 / and~e.0,1,32
:op1 (g / gene~e.29
:name (n3 / name :op1 "alpha"~e.30 :op2 "IIb"~e.31))
:op2 (g2 / gene~e.29
:name (n4 / name :op1 "beta3"))
:ARG1-of (s / specific-02~e.28
:ARG2 (c3 / cell
:name (n5 / name :op1 "platelet"~e.24)
:source (c4 / cell
:name (n6 / name :op1 "megakaryocyte"~e.26))))))))
# ::id bel_pmid_1008_0909.21272 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Using these methods , we found that JAK2 was essential for signal transduction but that loss of TYK2 made no appreciable difference in tyrosine phosphorylation of downstream molecules , including Mpl , STAT3 , and Shc ( 33 ) ..... In fact , tyrosine phosphorylation of STATs and DNA binding assays seem to be almost interchangeable measures of transcriptional activity .
# ::alignments 0-1.1.4 1-1.1.4.1.1 2-1.1.4.1 4-1.1.1 5-1.1 6-1.1.2.r 7-1.1.2.1.1.1.1 8-1.1.2.1.1.r 9-1.1.2.1 10-1.1.2.1.2.r 11-1.1.2.1.2.1 12-1.1.2.1.2 13-1.1.2 15-1.1.2.2.1 16-1.1.2.2.1.1.r 17-1.1.2.2.1.1.1.1 18-1.1.2.2 19-1.1.2.2.2.1.1.1 19-1.1.2.2.2.1.1.1.r 20-1.1.2.2.2.1.1 20-1.2.1.3.2.2 21-1.1.2.2.2 21-1.1.2.2.2.1.1.1 21-1.1.2.2.2.1.1.1.r 22-1.2.2 23-1.2.1.1.1.1.1 24-1.1.2.2.3 25-1.1.2.2.3.1.r 26-1.1.2.2.3.1.2.1 27-1.1.2.2.3.1.2 29-1.1.2.2.3.1.2.2 30-1.1.2.2.3.1.2.2.1.1.1.1 32-1.1.2.2.3.1.2.2.1.2.1.1 34-1.1.2.2.3.1.2.2.1 35-1.1.2.2.3.1.2.2.1.3.1.1 37-1.1.3.1.1.1 40-1.2.2 41-1.2.2 43-1.1.2.2.3.1.1.1 43-1.2.1.1.1.1.1 44-1.2.1.1 47-1.2.1 48-1.2.1.2.1.1.2.1 49-1.2.1.2.1 50-1.2.1.2 51-1.2 54-1.2.1.3.2.1 56-1.2.1.3 57-1.2.1.3.1.r 58-1.2.1.3.1.1 59-1.2.1.3.1
(m / multi-sentence
:snt1 (f / find-01~e.5
:ARG0 (w / we~e.4)
:ARG1~e.6 (c / contrast-01~e.13
:ARG1 (e / essential~e.9
:domain~e.8 (e2 / enzyme
:name (n / name :op1 "JAK2"~e.7))
:purpose~e.10 (t / transduce-01~e.12
:ARG1 (s / signal-07~e.11)))
:ARG2 (m2 / make-01~e.18
:ARG0 (l / lose-02~e.15
:ARG1~e.16 (e3 / enzyme
:name (n2 / name :op1 "TYK2"~e.17)))
:ARG1 (d / difference~e.21
:ARG1-of (a / appreciate-03
:ARG1-of (p9 / possible-01~e.20 :polarity~e.19,21 -~e.19,21)))
:ARG3 (p / phosphorylate-01~e.24
:ARG1~e.25 (a2 / amino-acid
:name (n3 / name :op1 "tyrosine"~e.43)
:part-of (m5 / molecule~e.27
:location (d2 / downstream~e.26)
:ARG2-of (i / include-01~e.29
:ARG1 (a3 / and~e.34
:op1 (p2 / protein
:name (n4 / name :op1 "Mpl"~e.30))
:op2 (p3 / protein
:name (n5 / name :op1 "STAT3"~e.32))
:op3 (p4 / protein
:name (n6 / name :op1 "Shc"~e.35)))))))))
:ARG1-of (d3 / describe-01
:ARG0 (p5 / publication
:ARG1-of (c2 / cite-01 :ARG2 33~e.37)))
:manner (u / use-01~e.0
:ARG1 (m3 / method~e.2
:mod (t2 / this~e.1))))
:snt2 (s3 / seem-01~e.51
:ARG1 (a4 / and~e.47
:op1 (p6 / phosphorylate-01~e.44
:ARG1 (a5 / amino-acid
:name (n7 / name :op1 "tyrosine"~e.23,43)
:part-of (p7 / protein
:name (n8 / name :op1 "STAT"))))
:op2 (a6 / assay-01~e.50
:ARG1 (b / bind-01~e.49
:ARG1 (n9 / nucleic-acid :wiki "DNA"
:name (n10 / name :op1 "DNA"~e.48))))
:ARG2-of (m4 / measure-01~e.56
:ARG1~e.57 (a7 / activity-06~e.59
:ARG1 (t3 / transcribe-01~e.58))
:ARG1-of (i3 / interchange-01
:mod (a8 / almost~e.54)
:ARG1-of (p8 / possible-01~e.20))))
:mod (i2 / in-fact~e.22,40,41)))
# ::id bel_pmid_1008_0909.24618 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok It has been difficult to interpret the physiologic role of STAT signaling in megakaryocyte development . In multiple cell lines it was reported that TPO induced activation of both STAT3 and STAT5 ( 5A and 5B ) ( 26 , 28?30 , 37 , 38 ) .... However , when purified murine megakaryocyte extracts were examined , we found that STAT3 was much more pronounced in both tyrosine phosphorylation and DNA binding activity than STAT5 ( 32 )
# ::alignments 2-1.1.1.r 3-1.1 5-1.1.1 7-1.1.1.1.1 8-1.1.1.1 9-1.1.1.1.2.r 10-1.1.1.1.2.1.1.1 11-1.1.1.1.2 12-1.1.1.1.3.r 13-1.1.1.1.3.1.1.1 14-1.1.1.1.3 17-1.2.3.1 18-1.2.3 19-1.2.3 22-1.2 23-1.2.1.r 24-1.2.1.1.1.1 25-1.2.1 26-1.2.1.2 27-1.2.1.2.1.r 28-1.2.1.2.1.3 29-1.2.1.2.1.1.1.1 30-1.2.1.2.1 30-1.2.2.1 31-1.2.1.2.1.2.1.1 33-1.2.2.1.1.1 34-1.2.2.1 34-1.2.2.1.3.1.1 35-1.2.2.1.2.1 38-1.2.2.1.3.1.1.1 42-1.2.2.1.3.1.1.4 44-1.2.2.1.3.1.1.5 47-1.3 49-1.3.1.3.r 50-1.3.1.3.1.1.2 51-1.3.1.3.1.1.1.1 52-1.3.1.3.1.1.1 53-1.3.1.3.1 53-1.3.1.3.1.1 53-1.3.1.3.1.1.r 55-1.3.1.3 57-1.3.1.1 58-1.3.1 59-1.3.1.2.r 60-1.3.1.2.1.1.1 62-1.3.1.2.2.1 63-1.3.1.2.2 64-1.3.1.2 65-1.3.1.2.3.r 66-1.3.1.2.3.3 67-1.3.1.2.3.1.1.1.1 68-1.3.1.2.3.1 69-1.3.1.2.3 70-1.3.1.2.3.2.1.1.2.1 71-1.3.1.2.3.2.1 72-1.3.1.2.3.2 73-1.3.1.2.4.r 74-1.3.1.2.4.1.1 76-1.3.2.1.1.1
(m / multi-sentence
:snt1 (d / difficult~e.3
:domain~e.2 (i / interpret-01~e.5
:ARG1 (r / role~e.8
:mod (p2 / physiologic~e.7)
:poss~e.9 (s / signal-07~e.11
:ARG0 (p3 / protein
:name (n / name :op1 "STAT"~e.10)))
:purpose~e.12 (d2 / develop-02~e.14
:ARG1 (c / cell
:name (n2 / name :op1 "megakaryocyte"~e.13))))))
:snt2 (r2 / report-01~e.22
:ARG1~e.23 (i2 / induce-01~e.25
:ARG0 (p4 / protein
:name (n3 / name :op1 "TPO"~e.24))
:ARG2 (a / activate-01~e.26
:ARG1~e.27 (a2 / and~e.30
:op1 (p5 / protein
:name (n4 / name :op1 "STAT3"~e.29))
:op2 (p6 / protein
:name (n5 / name :op1 "STAT5"~e.31))
:mod (b / both~e.28))))
:ARG1-of (d3 / describe-01
:ARG0 (a3 / and~e.30,34
:op1 (f / figure :mod "5A"~e.33)
:op2 (f2 / figure :mod "5B"~e.35)
:op3 (p7 / publication
:ARG1-of (c2 / cite-01
:ARG2 (a4 / and~e.34 :op1 26~e.38 :op2 28 :op3 30 :op4 37~e.42 :op5 38~e.44)))))
:location (c5 / cell-line~e.18,19
:quant (m5 / multiple~e.17)))
:snt3 (c6 / contrast-01~e.47
:ARG2 (f3 / find-01~e.58
:ARG0 (w / we~e.57)
:ARG1~e.59 (p / pronounced-02~e.64
:ARG1 (p9 / protein
:name (n6 / name :op1 "STAT3"~e.60))
:degree (m2 / more~e.63
:quant (m3 / much~e.62))
:condition~e.65 (a5 / and~e.69
:op1 (p10 / phosphorylate-01~e.68
:ARG1 (a6 / amino-acid
:name (n7 / name :op1 "tyrosine"~e.67)))
:op2 (a7 / activity-06~e.72
:ARG1 (b2 / bind-01~e.71
:ARG1 (n9 / nucleic-acid :wiki "DNA"
:name (n10 / name :op1 "DNA"~e.70))))
:mod (b3 / both~e.66))
:compared-to~e.73 (p11 / protein
:name (n8 / name :op1 "STAT5"~e.74)))
:time~e.49 (e / examine-01~e.55
:ARG1 (t / thing~e.53
:ARG1-of~e.53 (e2 / extract-01~e.53
:ARG2 (m6 / megakaryocyte~e.52
:mod (m4 / murine~e.51))
:ARG1-of (p13 / purify-01~e.50)))))
:ARG1-of (d5 / describe-01
:ARG0 (p12 / publication
:ARG1-of (c3 / cite-01 :ARG2 32~e.76)))))
# ::id bel_pmid_1008_5062.23884 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Activation of MEK1 and MEK2 involves phosphorylation upon conserved serine residues ( Ser @-@ 218 and Ser @-@ 222 on MEK1 , Ser @-@ 222 and Ser @-@ 226 on MEK2
# ::alignments 0-1.1 1-1.1.1.r 2-1.1.1.1.1.1 3-1.1.1 4-1.1.1.2.1.1 5-1 6-1.2 8-1.2.1.2 9-1.2.1.1.1.1 9-1.2.1.3.1.1.1.2.1 9-1.2.1.3.1.1.2.2.1 10-1.2.1 14-1.2.1.3.1.1.1.1 15-1.2.1.3.1 15-1.2.1.3.1.1 15-1.2.1.3.1.1.r 15-1.2.1.3.1.2 16-1.2.1.3.1.2.1.2.1 16-1.2.1.3.1.2.2.2.1 18-1.2.1.3.1.1.2.1 18-1.2.1.3.1.2.1.1 20-1.1.1.1.1.1 22-1.2.1.3.1.2.1.2.1 22-1.2.1.3.1.2.2.2.1 24-1.2.1.3.1.1.2.1 24-1.2.1.3.1.2.1.1 25-1.2.1.3.1 25-1.2.1.3.1.1 25-1.2.1.3.1.1.r 25-1.2.1.3.1.2 26-1.2.1.3.1.2.1.2.1 26-1.2.1.3.1.2.2.2.1 28-1.2.1.3.1.2.2.1 29-1.2.1.3.1.2.r 30-1.2.1.3.1.2.3
(i / involve-01~e.5
:ARG0 (a2 / activate-01~e.0
:ARG1~e.1 (a3 / and~e.3
:op1 (e / enzyme
:name (n2 / name :op1 "MEK1"~e.2,20))
:op2 (e2 / enzyme
:name (n3 / name :op1 "MEK2"~e.4))))
:ARG1 (p2 / phosphorylate-01~e.6
:ARG1 (r / residue~e.10
:mod (a4 / amino-acid
:name (n4 / name :op1 "serine"~e.9))
:ARG1-of (c / conserve-01~e.8)
:ARG1-of (m / mean-01
:ARG2 (a5 / and~e.15,25
:op1~e.15,25 (a6 / and~e.15,25
:op1 (a7 / amino-acid :mod 218~e.14
:name (n5 / name :op1 "serine"~e.9))
:op2 (a8 / amino-acid :mod 222~e.18,24
:name (n6 / name :op1 "serine"~e.9))
:part-of e)
:op2~e.29 (a9 / and~e.15,25
:op1 (a10 / amino-acid :mod 222~e.18,24
:name (n7 / name :op1 "serine"~e.16,22,26))
:op2 (a11 / amino-acid :mod 226~e.28
:name (n8 / name :op1 "serine"~e.16,22,26))
:part-of e2~e.30))))))
# ::id bel_pmid_1019_4465.17324 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok c @-@ Cbl is tyrosine @-@ phosphorylated , binds to Fyn upon insulin stimulation , and is translocated to small invaginations of the plasma membrane , called caveolae , after insulin stimulation
# ::alignments 0-1.1.1.2.1.1 2-1.1.1.2.1.1 4-1.1.1.1.1 6-1.1 8-1.2 9-1.2.2.r 10-1.2.2.1.1 12-1.2.3.1.1.1 13-1.2.3 15-1 17-1.3 18-1.3.2.r 19-1.3.2.2 20-1.3.2 21-1.3.2.1.r 23-1.3.2.1.1 24-1.3.2.1 26-1.3.2.1.2 27-1.3.2.1.2.1 29-1.3.3 30-1.3.3.1 31-1.3.3.1
(a / and~e.15
:op1 (p / phosphorylate-01~e.6
:ARG1 (a2 / amino-acid
:name (n2 / name :op1 "tyrosine"~e.4)
:part-of (p3 / protein
:name (n / name :op1 "c-Cbl"~e.0,2))))
:op2 (b / bind-01~e.8
:ARG1 p3
:ARG2~e.9 (e / enzyme
:name (n3 / name :op1 "Fyn"~e.10))
:condition (s / stimulate-01~e.13
:ARG2 (p4 / protein
:name (n4 / name :op1 "insulin"~e.12))))
:op3 (t / translocate-01~e.17
:ARG1 p3
:ARG2~e.18 (i / invaginate-01~e.20
:ARG1~e.21 (m / membrane~e.24
:mod (p2 / plasma~e.23)
:ARG1-of (c / call-01~e.26
:ARG2 (c2 / caveolae~e.27)))
:mod (s2 / small~e.19))
:time (a3 / after~e.29
:op1 s~e.30,31)))
# ::id bel_pmid_1019_4465.17346 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Insulin and IGF @-@ 1 stimulation also promote association between IRS @-@ 1 and aVb3 integrin ( vitronectin receptor )
# ::alignments 0-1.1.1.1.1.1 1-1.1.1 2-1.1.1.2.1.1 4-1.1.1.2.1.1 5-1.1 6-1.3 7-1 8-1.2 10-1.2.2.1.1 12-1.2.2.1.1 14-1.2.3.1.1 15-1.2.3.1.2 17-1.2.3.2.1.1.1.1 18-1.2.3.2.1
(p / promote-01~e.7
:ARG0 (s / stimulate-01~e.5
:ARG1 (a2 / and~e.1
:op1 (p6 / protein
:name (n5 / name :op1 "insulin"~e.0))
:op2 (p3 / protein
:name (n2 / name :op1 "IGF-1"~e.2,4))))
:ARG1 (a3 / associate-01~e.8
:ARG0 a2
:ARG1 (p2 / protein
:name (n3 / name :op1 "IRS-1"~e.10,12))
:ARG2 (p5 / protein
:name (n6 / name :op1 "aVb3"~e.14 :op2 "integrin"~e.15)
:ARG1-of (d / describe-01
:ARG2 (r / receptor~e.18
:mod (p4 / protein
:name (n / name :op1 "vitronectin"~e.17))))))
:mod (a / also~e.6))
# ::id bel_pmid_1019_4465.17828 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Thiazolidinediones ( TZDs ) , the class of insulin sensitizers that act through the nuclear receptor PPAR @-@ g , increase CAP expression levels and c @-@ Cbl phosphorylation significantly in adipocytes ( 54 ) , possibly contributing to their insulin sensitizing effect
# ::alignments 6-1.1.1 7-1.1.1.1.r 8-1.1.1.1.1.1.1.1 11-1.1.1.1 11-1.1.1.1.2 11-1.1.1.1.2.r 14-1.1.1.1.2.1.2 15-1.1.1.1.2.1 16-1.1.1.1.2.1.1.1 18-1.1.1.1.2.1.1.1 20-1 21-1.2.1.1.1.1.1 22-1.2.1.1 23-1.2.1 24-1.2 25-1.2.2.1.1.1 27-1.2.2.1.1.1 28-1.2.2 29-1.3 33-1.5.1.1.1 36-1.6.2 37-1.6 40-1.1.1.1.1.1.1.1 41-1.1.1.1.1 41-1.6.1.1 42-1.6.1
(i / increase-01~e.20
:ARG0 (t / thiazolidinedione
:mod (c / class~e.6
:mod~e.7 (m / molecular-physical-entity~e.11
:ARG0-of (s / sensitize-01~e.41
:ARG1 (p2 / protein
:name (n3 / name :op1 "insulin"~e.8,40)))
:ARG0-of~e.11 (a / act-01~e.11
:instrument (r / receptor~e.15
:name (n2 / name :op1 "PPAR-g"~e.16,18)
:mod (n / nucleus~e.14))))))
:ARG1 (a2 / and~e.24
:op1 (l / level~e.23
:degree-of (e / express-03~e.22
:ARG2 (p5 / protein
:name (n6 / name :op1 "CAP"~e.21))))
:op2 (p3 / phosphorylate-01~e.28
:ARG1 (p6 / protein
:name (n4 / name :op1 "c-Cbl"~e.25,27))))
:ARG2 (s2 / significant-02~e.29)
:location (c2 / cell
:name (n5 / name :op1 "adipocyte"))
:ARG1-of (d / describe-01
:ARG0 (p4 / publication
:ARG1-of (c4 / cite-01 :ARG2 54~e.33)))
:ARG0-of (c3 / contribute-01~e.37
:ARG1 (a3 / affect-01~e.42
:ARG2 (s3 / sensitize-01~e.41
:ARG0 t
:ARG1 p2))
:ARG1-of (p / possible-01~e.36)))
# ::id bel_pmid_1019_4465.19902 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Interestingly , this NPXY sequence is also a receptor internalization motif found in many members of the tyrosine kinase receptor family , the low @-@ density lipoprotein receptor ( 11 @-@ 13 ) , and the transferrin receptor ( 14 ) , all of which are internalized in a ligand @-@ dependent fashion .
# ::alignments 0-1.4 2-1.2.2 3-1.2.1.1 4-1.2 5-1.2.r 6-1.5 8-1.1.1 9-1.1 10-1 11-1.3 12-1.3.1.r 13-1.3.1.1 14-1.3.1 17-1.3.1.2.1.1.1 18-1.3.1.2.1.1.2 19-1.3.1.2.1.1.3 20-1.3.1.2.1 23-1.3.1.4.1.1.1 25-1.3.1.4.1.1.1 26-1.3.1.4.1.1.2 27-1.3.1.4.1.1.3 29-1.3.1.4.1.2.1.1.1.1 31-1.3.1.4.1.2.1.1.1.2 34-1.3.1.4 36-1.3.1.4.2.1.1 37-1.3.1.4.2.1.2 39-1.3.1.4.2.2.1.1.1 46-1.3.1.3 47-1.3.1.3.1.r 49-1.3.1.3.1.1 51-1.3.1.3.1
(m / motif~e.10
:ARG0-of (i / internalize-01~e.9
:ARG1 (r / receptor~e.8))
:domain~e.5 (d / dna-sequence~e.4
:name (n / name :op1 "NPXY"~e.3)
:mod (t / this~e.2))
:ARG1-of (f2 / find-01~e.11
:location~e.12 (m2 / member~e.14
:quant (m3 / many~e.13)
:ARG1-of (i2 / include-91
:ARG2 (p / protein-family~e.20
:name (n2 / name :op1 "tyrosine"~e.17 :op2 "kinase"~e.18 :op3 "receptor"~e.19)))
:ARG1-of (i4 / internalize-01~e.46
:manner~e.47 (d4 / depend-01~e.51
:ARG1 (l / ligand~e.49)))
:example (a / and~e.34
:op1 (p2 / protein
:name (n3 / name :op1 "low-density"~e.23,25 :op2 "lipoprotein"~e.26 :op3 "receptor"~e.27)
:ARG1-of (d2 / describe-01
:ARG0 (p3 / publication
:ARG1-of (c / cite-01
:ARG2 (v / value-interval :op1 11~e.29 :op2 13~e.31)))))
:op2 (p4 / protein
:name (n4 / name :op1 "transferrin"~e.36 :op2 "receptor"~e.37)
:ARG1-of (d3 / describe-01
:ARG0 (p5 / publication
:ARG1-of (c2 / cite-01 :ARG2 14~e.39)))))))
:ARG2-of (i3 / interest-01~e.0)
:mod (a2 / also~e.6))
# ::id bel_pmid_1019_4465.19968 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Csk has been reported to associate with IRS @-@ 1 through its SH2 domain and promote dephosphorylation of the focal adhesion kinase ( FAK ) in an insulin @-@ dependent manner ( 56 ) .
# ::alignments 0-1.1.1.1.2.1.1 3-1 5-1.1.1 6-1.1.1.2.r 7-1.1.1.2.1.1 9-1.1.1.2.1.1 12-1.1.1.1.1.1 13-1.1.1.1.1.2 14-1.1 15-1.1.2 16-1.1.2.2 17-1.1.2.2.1.r 19-1.1.2.2.1.1.1 20-1.1.2.2.1.1.2 21-1.1.2.2.1.1.3 27-1.1.2.2.2.1.1.1 29-1.1.2.2.2 30-1.1.2.2.2.r 32-1.2.1.1.1
(r / report-01~e.3
:ARG1 (a / and~e.14
:op1 (a2 / associate-01~e.5
:ARG1 (p6 / protein-segment
:name (n6 / name :op1 "SH2"~e.12 :op2 "domain"~e.13)
:part-of (p / protein
:name (n / name :op1 "Csk"~e.0)))
:ARG2~e.6 (p2 / protein
:name (n2 / name :op1 "IRS-1"~e.7,9)))
:op2 (p3 / promote-01~e.15
:ARG0 p
:ARG1 (d2 / dephosphorylate-01~e.16
:ARG1~e.17 (e / enzyme
:name (n4 / name :op1 "focal"~e.19 :op2 "adhesion"~e.20 :op3 "kinase"~e.21))
:manner~e.30 (d4 / depend-01~e.29
:ARG1 (p7 / protein
:name (n3 / name :op1 "insulin"~e.27))))))
:ARG1-of (d5 / describe-01
:ARG0 (p5 / publication
:ARG1-of (c / cite-01 :ARG2 56~e.32))))
# ::id bel_pmid_1019_4465.20030 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In smooth muscle cells , blocking ligand occupancy of aVb3 integrin reduces IGF @-@ 1 @-@ induced IRS @-@ 1 phosphorylation
# ::alignments 1-1.3.1.1 2-1.3.1 3-1.3 5-1.1 6-1.1.1.1 9-1.1.1.2.1.1 10-1.1.1.2 11-1 12-1.2.2.1.1.1 14-1.2.2.1.1.1 16-1.2.2 17-1.2.1.1.1 19-1.2.1.1.1 20-1.2
(r / reduce-01~e.11
:ARG0 (b / block-01~e.5
:ARG1 (o / occupy-01
:ARG0 (l / ligand~e.6)
:ARG1 (i2 / integrin~e.10
:name (n / name :op1 "aVb3"~e.9))))
:ARG1 (p / phosphorylate-01~e.20
:ARG1 (p2 / protein
:name (n2 / name :op1 "IRS-1"~e.17,19))
:ARG2-of (i / induce-01~e.16
:ARG0 (p3 / protein
:name (n3 / name :op1 "IGF-1"~e.12,14))))
:location (c / cell~e.3
:mod (m / muscle~e.2
:ARG1-of (s / smooth-06~e.1))))
# ::id bel_pmid_1019_4465.20066 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Nck associates with IRS @-@ 1 ( 45 ) , many different tyrosine kinases , several serine @/@ threonine kinases through its SH2 domain , as well as Sos through its SH3 domains
# ::alignments 0-1.1.2.1.1 1-1 2-1.3.r 3-1.3.1.1 5-1.3.1.1 7-1.4.1.1.1 10-1.2.1.2 11-1.2.1 11-1.2.1.3 11-1.2.1.3.r 12-1.2.1.1.1 13-1.2.1.1.2 15-1.2.2.3 16-1.2.2.1.1.1 18-1.2.2.2.1.1 19-1.2.1.1.2 19-1.2.2.1.1.2 19-1.2.2.2.1.2 22-1.1.1.1 23-1.1.1.2 25-1.2 26-1.2 27-1.2 27-1.2.r 28-1.2.3.2.1.1 31-1.2.3.1.1 32-1.2.3.1.2
(a / associate-01~e.1
:ARG0 (p3 / protein-segment
:name (n8 / name :op1 "SH2"~e.22 :op2 "domain"~e.23)
:part-of (p / protein
:name (n / name :op1 "Nck"~e.0)))
:ARG1~e.27 (a2 / and~e.25,26,27
:op1 (e / enzyme~e.11
:name (n2 / name :op1 "tyrosine"~e.12 :op2 "kinase"~e.13,19)
:quant (m / many~e.10)
:ARG1-of~e.11 (d / differ-02~e.11))
:op2 (o / or
:op1 (e2 / enzyme
:name (n3 / name :op1 "serine"~e.16 :op2 "kinase"~e.19))
:op2 (e3 / enzyme
:name (n4 / name :op1 "threonine"~e.18 :op2 "kinase"~e.19))
:quant (s / several~e.15))
:op3 (p4 / protein-segment
:name (n9 / name :op1 "SH3"~e.31 :op2 "domain"~e.32)
:part-of (p2 / protein
:name (n6 / name :op1 "Sos"~e.28))))
:ARG2~e.2 (p5 / protein
:name (n5 / name :op1 "IRS-1"~e.3,5))
:ARG1-of (d2 / describe-01
:ARG0 (p6 / publication
:ARG1-of (c / cite-01 :ARG2 45~e.7))))
# ::id bel_pmid_1019_4465.21192 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Gab @-@ 1 is heavily phosphorylated by the epidermal growth factor receptor , but poorly by the insulin receptor
# ::alignments 0-1.1.1.1.1 2-1.1.1.1.1 4-1.1.3 5-1.1 5-1.2 6-1.1.2.r 8-1.1.2.1.1 9-1.1.2.1.2 10-1.1.2.1.3 11-1.1.2.1.4 13-1 14-1.2.3 15-1.2.2.r 17-1.2.2.1.1.1 18-1.2.2
(c / contrast-01~e.13
:ARG1 (p / phosphorylate-01~e.5
:ARG1 (p4 / protein
:name (n2 / name :op1 "Gab-1"~e.0,2))
:ARG2~e.6 (e / enzyme
:name (n / name :op1 "epidermal"~e.8 :op2 "growth"~e.9 :op3 "factor"~e.10 :op4 "receptor"~e.11))
:degree (h2 / heavy~e.4))
:ARG2 (p2 / phosphorylate-01~e.5
:ARG1 p4
:ARG2~e.15 (r / receptor~e.18
:mod (p5 / protein
:name (n3 / name :op1 "insulin"~e.17)))
:degree (p3 / poor~e.14)))
# ::id bel_pmid_1019_4465.21226 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Recently , it was shown that Fyn is one of the kinases responsible for the phosphorylation of caveolin
# ::alignments 0-1.2 4-1 5-1.1.r 6-1.1.1.1 11-1.1.2.1 12-1.1.2.1.1 13-1.1.2.1.1.1.r 15-1.1.2.1.1.1 16-1.1.2.1.1.1.1.r 17-1.1.2.1.1.1.1.1.1
(s / show-01~e.4
:ARG1~e.5 (e / enzyme
:name (n / name :op1 "Fyn"~e.6)
:ARG1-of (i / include-91
:ARG2 (k / kinase~e.11
:ARG0-of (r / responsible-01~e.12
:ARG1~e.13 (p / phosphorylate-01~e.15
:ARG1~e.16 (p2 / protein
:name (n2 / name :op1 "caveolin"~e.17)))))))
:time (r2 / recent~e.0))
# ::id bel_pmid_1019_4465.21256 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok It also contains an additional binding site located in the phosphorylated kinase activation loop of the insulin receptor but is only very slightly phosphorylated by insulin receptor .
# ::alignments 0-1.1.1 1-1.1.3 2-1.1 4-1.1.2.2 5-1.1.2.3 6-1.1.2 7-1.1.2.1.r 10-1.1.2.1.1.1.1 11-1.1.2.1.1.1 12-1.1.2.1.1 13-1.1.2.1 14-1.1.2.1.2.r 16-1.1.2.1.2.1.1.1 17-1.1.2.1.2 18-1 20-1.2.3.2 21-1.2.3.1 22-1.2.3 23-1.2 24-1.2.2.r 25-1.2.2 26-1.2.2
(h / have-concession-91~e.18
:ARG1 (c / contain-01~e.2
:ARG0 (i / it~e.0)
:ARG1 (p3 / protein-segment~e.6
:location~e.7 (l2 / loop~e.13
:ARG0-of (a / activate-01~e.12
:ARG1 (k / kinase~e.11
:ARG3-of (p / phosphorylate-01~e.10)))
:poss~e.14 (r2 / receptor~e.17
:mod (p4 / protein
:name (n / name :op1 "insulin"~e.16))))
:mod (a2 / additional~e.4)
:ARG1-of (b / bind-01~e.5))
:mod (a3 / also~e.1))
:ARG2 (p2 / phosphorylate-01~e.23
:ARG1 i
:ARG2~e.24 r2~e.25,26
:degree (s2 / slight~e.22
:degree (v / very~e.21)
:mod (o / only~e.20))))
# ::id bel_pmid_1019_4465.22614 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Crk has been reported to associate with tyrosine @-@ phosphorylated proteins , such as p130Cas and paxillin ( 42 , 43 ) , involved in the rearrangement of cytoskeletal components , through its SH2 domain .
# ::alignments 0-1.1.1.1.1 3-1 5-1.1 6-1.1.2.4.2.r 7-1.1.2.2.1.1 9-1.1.2.3 10-1.1.2 12-1.1.2.1.r 13-1.1.2.1.r 14-1.1.2.1.1.1.1 15-1.1.2.1 15-1.1.2.1.3.1.1.1 16-1.1.2.1.2.1.1 18-1.1.2.1.3.1.1.1.1 20-1.1.2.1.3.1.1.1.2 23-1.1.2.4 24-1.1.2.4.1.r 26-1.1.2.4.1 29-1.1.2.4.1.1 32-1.1.2.4.2.2 32-1.1.2.4.2.2.r 33-1.1.2.4.2.1.1 34-1.1.2.4.2.1.2
(r / report-01~e.3
:ARG1 (a / associate-01~e.5
:ARG1 (p / protein
:name (n / name :op1 "Crk"~e.0))
:ARG2 (p2 / protein~e.10
:example~e.12,13 (a3 / and~e.15
:op1 (p4 / protein
:name (n3 / name :op1 "p130Cas"~e.14))
:op2 (p5 / protein
:name (n4 / name :op1 "paxillin"~e.16))
:ARG1-of (d / describe-01
:ARG0 (p6 / publication
:ARG1-of (c / cite-01
:ARG2 (a4 / and~e.15 :op1 42~e.18 :op2 43~e.20)))))
:part (a2 / amino-acid
:name (n2 / name :op1 "tyrosine"~e.7))
:ARG1-of (p3 / phosphorylate-01~e.9)
:ARG1-of (i / involve-01~e.23
:ARG2~e.24 (r2 / rearrange-01~e.26
:ARG1 (c2 / component~e.29
:part-of (c3 / cytoskeleton)))
:instrument~e.6 (p7 / protein-segment
:name (n5 / name :op1 "SH2"~e.33 :op2 "domain"~e.34)
:part-of~e.32 p~e.32)))))
# ::id bel_pmid_1019_4465.22706 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok c @-@ Cbl associated protein ( CAP ) that has three sequential SH3 domains is specifically expressed in insulin @-@ responsive cell types and associates with both c @- Cbl and the insulin receptor
# ::alignments 0-1.1.1.1.1 2-1.1.1.1.1 3-1.1.1.1.2 3-1.2 4-1.1.1.1.3 9-1.1.1 9-1.1.1.2 9-1.1.1.2.r 10-1.1.1.2.1.1 11-1.1.1.2.1.3 12-1.1.1.2.1.2.1 13-1.1.1.2.1.2.2 15-1.1.3 16-1.1 17-1.1.2.r 18-1.1.2.1.1.1.1.1 20-1.1.2.1.1 21-1.1.2.1 22-1.1.2 23-1 24-1.2 27-1.2.2.1.1.1 29-1.2.2.1.1.1 30-1.2.2 32-1.2.2.2.1 33-1.2.2.2
(a / and~e.23
:op1 (e / express-03~e.16
:ARG2 (p / protein~e.9
:name (n / name :op1 "c-Cbl"~e.0,2 :op2 "associated"~e.3 :op3 "protein"~e.4)
:ARG0-of~e.9 (h / have-03~e.9
:ARG1 (p2 / protein-segment :quant 3~e.10
:name (n2 / name :op1 "SH3"~e.12 :op2 "domain"~e.13)
:mod (s / sequential~e.11))))
:ARG3~e.17 (t / type-03~e.22
:ARG1 (c / cell~e.21
:ARG0-of (r / responsive-02~e.20
:ARG1 (p4 / protein
:name (n4 / name :op1 "insulin"~e.18)))))
:ARG1-of (s2 / specific-02~e.15))
:op2 (a2 / associate-01~e.3,24
:ARG1 p
:ARG2 (a3 / and~e.30
:op1 (p3 / protein
:name (n3 / name :op1 "c-Cbl"~e.27,29))
:op2 (r2 / receptor~e.33
:mod p4~e.32))))
# ::id bel_pmid_1019_4465.22914 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Recently , phosphorylated p62 dok was demonstrated to associate with the GTPase @-@ activating protein ( GAP ) for Ras .
# ::alignments 0-1.2 2-1.1.1.2 6-1 8-1.1 9-1.1.2.r 11-1.1.2.1.1 13-1.1.2.1.1 14-1.1.2.1.2 18-1.1.3.r 19-1.1.3.1.1
(d / demonstrate-01~e.6
:ARG1 (a / associate-01~e.8
:ARG1 (p / protein
:name (n2 / name :op1 "p62dok")
:ARG3-of (p2 / phosphorylate-01~e.2))
:ARG2~e.9 (p3 / protein
:name (n3 / name :op1 "GTPase-activating"~e.11,13 :op2 "protein"~e.14))
:beneficiary~e.18 (p4 / protein-family
:name (n / name :op1 "Ras"~e.19)))
:time (r / recent~e.0))
# ::id bel_pmid_1019_4465.23034 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In the case of insulin , it is unclear whether SHIP associates with IRS proteins or the insulin receptor , although a recent report has demonstrated SHIP association with IRS @-@ 2 in response to erythropoietin
# ::alignments 4-1.1.1.1.1 8-1.1.2 8-1.1.2.1 8-1.1.2.1.r 9-1.1.2.2.1 9-1.1.2.2.1.r 10-1.1.2.2.2.1.1 11-1.1.2.2 12-1.1.2.2.3.r 13-1.1.2.2.3.1.1.1 14-1.1.1 14-1.1.2.2.2 14-1.1.2.2.3.1 14-1.2.2.2 15-1.1.2.2.3 17-1.1.2.2.3.2.1 18-1.1.2.2.3.2 20-1 22-1.2.1.1 23-1.2.1 25-1.2 26-1.1.2.2.2.1.1 27-1.2.2 29-1.2.2.2.1.1 31-1.2.2.2.1.1 32-1.2.2.3.r 33-1.2.2.3 34-1.2.2.3.1.r 35-1.2.2.3.1
(h / have-concession-91~e.20
:ARG1 (e / exemplify-01
:ARG0 (p4 / protein~e.14
:name (n / name :op1 "insulin"~e.4))
:ARG1 (c / clear-06~e.8 :polarity~e.8 -~e.8
:ARG1 (a / associate-01~e.11 :mode~e.9 interrogative~e.9
:ARG1 (p2 / protein~e.14
:name (n3 / name :op1 "SHIP"~e.10,26))
:ARG2~e.12 (o / or~e.15
:op1 (p / protein~e.14
:name (n2 / name :op1 "IRS"~e.13))
:op2 (r / receptor~e.18
:mod p4~e.17)))))
:ARG2 (d / demonstrate-01~e.25
:ARG0 (r2 / report~e.23
:time (r3 / recent~e.22))
:ARG1 (a2 / associate-01~e.27
:ARG1 p
:ARG2 (p3 / protein~e.14
:name (n4 / name :op1 "IRS-2"~e.29,31))
:ARG2-of~e.32 (r4 / respond-01~e.33
:ARG1~e.34 (e2 / erythropoietin~e.35)))))
# ::id bel_pmid_1019_4465.23202 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The SH2 domain of the adaptor protein Grb @- 2 and the SH2 domain of the phosphotyrosine phosphatase SHP @-@ 2 bind other sequences , including pYVNI , pYIDL , and pYASI sequences ( 1 ) .
# ::alignments 1-1.1.1.1.1 1-1.1.2.1.1 2-1.1.1.1.2 2-1.1.2.1.2 5-1.1.1.2.2 6-1.1.1 6-1.1.1.2 6-1.1.1.2.r 6-1.1.2 6-1.1.2.2 6-1.1.2.2.r 6-1.2.1.1.1 6-1.2.1.1.2 6-1.2.1.1.3 9-1.1.2.2.1.3 12-1.1.2.1.1 13-1.1.2.1.2 16-1.1.2.2.1.1 17-1.1.2.2.1.2 18-1.1.2.2.1.3 20-1.1.2.2.1.3 21-1 22-1.2.2 23-1.2 25-1.2.1 26-1.2.1.1.1.1.1 28-1.2.1.1.2.1.1 30-1.2.1.1 31-1.2.1.1.3.1.1 32-1.2 34-1.3.1.1.1
(b / bind-01~e.21
:ARG1 (a / and
:op1 (p7 / protein-segment~e.6
:name (n8 / name :op1 "SH2"~e.1 :op2 "domain"~e.2)
:part-of~e.6 (p / protein~e.6
:name (n2 / name :op1 "Grb2")
:mod (a2 / adaptor~e.5)))
:op2 (p8 / protein-segment~e.6
:name (n / name :op1 "SH2"~e.1,12 :op2 "domain"~e.2,13)
:part-of~e.6 (p2 / protein~e.6
:name (n4 / name :op1 "phosphotyrosine"~e.16 :op2 "phosphatase"~e.17 :op3 "SHP-2"~e.9,18,20))))
:ARG2 (s / sequence~e.23,32
:ARG2-of (i / include-91~e.25
:ARG1 (a3 / and~e.30
:op1 (p3 / protein-segment~e.6
:name (n5 / name :op1 "pYVNI"~e.26))
:op2 (p4 / protein-segment~e.6
:name (n6 / name :op1 "pYIDL"~e.28))
:op2 (p5 / protein-segment~e.6
:name (n7 / name :op1 "pYASI"~e.31))))
:mod (o / other~e.22))
:ARG1-of (d3 / describe-01
:ARG0 (p6 / publication
:ARG1-of (c / cite-01 :ARG2 1~e.34))))
# ::id bel_pmid_1019_4465.23382 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Since an inhibitor against SERCA induces apoptosis in some cell lines ( 76 ) , the IRS @/@ SERCA complex might be involved in an insulin and IGF @-@ 1 @-@ dependent antiapoptotic effect .
# ::alignments 0-1 2-1.1.1 2-1.1.1.1 2-1.1.1.1.r 3-1.2.1.2.1 4-1.1.1.1.1.1.1 5-1.1 6-1.1.2 6-1.2.1.2.1.1 7-1.1.4.r 8-1.1.4.1 9-1.1.4 10-1.1.4 12-1.1.3.1.1.1 16-1.2.1.1.1.1.1 18-1.2.1.1.2 19-1.2.1.1 20-1.2 22-1.2.1 25-1.2.1.2.2.1.1.1.1 26-1.2.1.2.2.1 27-1.2.1.2.2.1.2.1.1 29-1.2.1.2.2.1.2.1.1 31-1.2.1.2.2 33-1.2.1.2
(c / cause-01~e.0
:ARG0 (i2 / induce-01~e.5
:ARG0 (m2 / molecular-physical-entity~e.2
:ARG0-of~e.2 (i / inhibit-01~e.2
:ARG1 (p2 / protein
:name (n / name :op1 "SERCA"~e.4))))
:ARG2 (a / apoptosis~e.6)
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c4 / cite-01 :ARG2 76~e.12)))
:location~e.7 (c3 / cell-line~e.9,10
:mod (s / some~e.8)))
:ARG1 (p / possible-01~e.20
:ARG1 (i3 / involve-01~e.22
:ARG1 (m / macro-molecular-complex~e.19
:part (p4 / protein
:name (n2 / name :op1 "IRS"~e.16))
:part p2~e.18)
:ARG2 (a2 / affect-01~e.33
:ARG2 (c2 / counter-01~e.3
:ARG1 (a5 / apoptosis~e.6))
:ARG0-of (d2 / depend-01~e.31
:ARG1 (a4 / and~e.26
:op1 (p5 / protein
:name (n3 / name :op1 "insulin"~e.25))
:op2 (p6 / protein
:name (n5 / name :op1 "IGF-1"~e.27,29))))))))
# ::id bel_pmid_1019_4465.23752 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Grb @-@ IR is a recently discovered SH2 domain protein that may translocate from the cytosol to the plasma membrane and bind directly to the tyrosine @-@ phosphorylated insulin receptor
# ::alignments 0-1.3.1.1 2-1.3.1.1 3-1.3.r 5-1.2.1 6-1.2 7-1.1.1.1 8-1.1.1.2 9-1 11-1.4.3 12-1.4 13-1.4.2.r 15-1.4.2 16-1.4.1.r 18-1.4.1.1 19-1.4.1 21-1.5 22-1.5.2 23-1.5.1.r 25-1.5.1.2.1.1 27-1.5.1.1.1 28-1.5.1.1 29-1.5.1
(p6 / protein~e.9
:part (p5 / protein-segment
:name (n2 / name :op1 "SH2"~e.7 :op2 "domain"~e.8))
:ARG1-of (d2 / discover-01~e.6
:time (r / recent~e.5))
:domain~e.3 (p2 / protein
:name (n / name :op1 "Grb-IR"~e.0,2))
:ARG1-of (t / translocate-01~e.12
:ARG2~e.16 (m / membrane~e.19
:mod (p3 / plasma~e.18))
:ARG3~e.13 (c / cytosol~e.15)
:ARG1-of (p / possible-01~e.11))
:ARG1-of (b / bind-01~e.21
:ARG2~e.23 (r2 / receptor~e.29
:mod (i / insulin~e.28
:ARG1-of (p4 / phosphorylate-01~e.27))
:part (a2 / amino-acid
:name (n4 / name :op1 "tyrosine"~e.25)))
:ARG1-of (d / direct-02~e.22)
:ARG1-of p))
# ::id bel_pmid_1019_4465.23766 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The physiological substrates for SHP @- 2 are not known , but overexpression of SHP @-@ 2 modulates cell adhesion and migration , as well as insulin activation of the Ras @/@ MAP @-@ kinase pathway Several isoforms of 14 @-@ 3 @-@ 3 proteins ( b , e, and z ) have also been shown to associate with IRS @-@ 1 , presumably through one of the several RXRXXpS motifs of IRS @-@ 1 .
# ::alignments 1-1.1.1.2.1 2-1.1.1.2 4-1.1.1.2.2.1.1 6-1.1.1.2.2.1.1 8-1.1.1.1 8-1.1.1.1.r 9-1.1.1 11-1.1 12-1.1.2.1.1 13-1.1.2.1.1.1.r 14-1.1.2.1.1.1 15-1.1.2.1.1.1 16-1.1.2.1.1.1 17-1.1.2.1 18-1.1.2.1.2.1.1.1 19-1.1.2.1.2.1.1 20-1.1.2.1.2.1 21-1.1.2.1.2.1.2 23-1.1.2.1.2.1 24-1.1.2.1.2.1 25-1.1.2.1.2 25-1.1.2.1.2.r 26-1.1.2.1.2.2.1 27-1.1.2.1.2.2 28-1.1.2.1.2.2.2.r 30-1.1.2.1.2.2.2.1.1 32-1.1.2.1.2.2.2.1.1 34-1.1.2.1.2.2.2.1.1 35-1.1.2.1.2.2.2 36-1.2.1.1.3 37-1.2.1.1 39-1.2.1.1.1.1.1 39-1.2.1.1.2.1.1.1.1 39-1.2.1.1.2.1.2.1.1 39-1.2.1.1.2.1.3.1.1 41-1.2.1.1.1.1.1 41-1.2.1.1.2.1.1.1.1 41-1.2.1.1.2.1.2.1.1 41-1.2.1.1.2.1.3.1.1 43-1.2.1.1.1.1.1 43-1.2.1.1.2.1.1.1.1 43-1.2.1.1.2.1.2.1.1 43-1.2.1.1.2.1.3.1.1 44-1.1.1.2.2 44-1.2.1.1.1 44-1.2.1.1.2.1.1 44-1.2.1.1.2.1.2 44-1.2.1.1.2.1.3 44-1.2.1.2 49-1.2.1.1.2.1 53-1.2.2 55-1.2 57-1.2.1 58-1.2.1.3.r 59-1.2.1.2.1.1 61-1.2.1.2.1.1 63-1.2.1.3.2 65-1.2.1.2.1.1 68-1.2.1.1.3 69-1.2.1.3.1.1.1.1 70-1.2.1.3 70-1.2.1.3.1.1 72-1.2.1.2.1.1 74-1.2.1.2.1.1
(m3 / multi-sentence
:snt1 (c / contrast-01~e.11
:ARG1 (k / know-01~e.9 :polarity~e.8 -~e.8
:ARG1 (s / substrate~e.2
:mod (p2 / physiology~e.1)
:topic (p3 / protein~e.44
:name (n2 / name :op1 "SHP-2"~e.4,6))))
:ARG2 (a / and
:op1 (m / modulate-01~e.17
:ARG0 (o / overexpress-01~e.12
:ARG1~e.13 p3~e.14,15,16)
:ARG1~e.25 (a4 / and~e.25
:op1 (a2 / and~e.20,23,24
:op1 (a3 / adhere-01~e.19
:ARG1 (c2 / cell~e.18))
:op2 (m2 / migrate-01~e.21
:ARG0 c2))
:op2 (a5 / activate-01~e.27
:ARG0 (i3 / insulin~e.26)
:ARG1~e.28 (p4 / pathway~e.35
:name (n3 / name :op1 "Ras/MAP-kinase"~e.30,32,34)))))))
:snt2 (s2 / show-01~e.55
:ARG1 (a8 / associate-01~e.57
:ARG1 (i / isoform~e.37
:mod (p / protein~e.44
:name (n / name :op1 "14-3-3"~e.39,41,43))
:ARG1-of (d / describe-01
:ARG2 (a7 / and~e.49
:op1 (p5 / protein~e.44
:name (n4 / name :op1 "14-3-3β"~e.39,41,43))
:op2 (p8 / protein~e.44
:name (n5 / name :op1 "14-3-3ε"~e.39,41,43))
:op3 (p9 / protein~e.44
:name (n8 / name :op1 "14-3-3ζ"~e.39,41,43))))
:quant (s3 / several~e.36,68))
:ARG2 (p6 / protein~e.44
:name (n6 / name :op1 "IRS-1"~e.59,61,65,72,74))
:instrument~e.58 (m5 / motif~e.70
:ARG1-of (i2 / include-91
:ARG2 (m4 / motif~e.70
:name (n7 / name :op1 "RXRXXpS"~e.69)
:part-of p6))
:ARG1-of (p7 / presume-01~e.63)))
:mod (a6 / also~e.53)))
# ::id bel_pmid_1019_4465.23768 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok TNF @-@ a appears to impair insulin signaling by increasing serine phosphorylation of IRS @-@ 1 . Serine @-@ phosphorylated IRS @-@ 1 inhibits insulin receptor tyrosine kinase activity , which leads to impaired downstream signaling
# ::alignments 0-1.1.1.1.1.1 2-1.1.1.1.1.1 3-1.1 5-1.1.1 6-1.1.1.2.1 7-1.1.1.2 8-1.1.1.3.r 9-1.1.1.3 10-1.1.1.3.2.1.1.1 11-1.1.1.3.2 13-1.1.1.3.2.1.2.1.1 13-1.2.1.1.2.1.1 15-1.1.1.3.2.1.2.1.1 15-1.2.1.1.2.1.1 17-1.1.1.3.2.1.1.1 17-1.2.1.1.1.1 19-1.2.1 20-1.2.1.1.2.1.1 22-1.2.1.1.2.1.1 23-1.2 24-1.2.2.1.2 25-1.2.2.1.1.1 26-1.2.2.1.1.2 27-1.2.2.1.1.3 28-1.2.2 31-1.2.3 32-1.2.3.1.r 33-1.2.3.1.2 34-1.2.3.1.1 35-1.2.3.1
(m / multi-sentence
:snt1 (a2 / appear-02~e.3
:ARG1 (i / impair-01~e.5
:ARG0 (p2 / protein
:name (n2 / name :op1 "TNF-a"~e.0,2))
:ARG1 (s / signal-07~e.7
:ARG1 (i5 / insulin~e.6))
:manner~e.8 (i2 / increase-01~e.9
:ARG0 p2
:ARG1 (p3 / phosphorylate-01~e.11
:ARG1 (a / amino-acid
:name (n / name :op1 "serine"~e.10,17)
:part-of (p4 / protein
:name (n4 / name :op1 "IRS-1"~e.13,15)))))))
:snt2 (i3 / inhibit-01~e.23
:ARG0 (p6 / phosphorylate-01~e.19
:ARG1 (a4 / amino-acid
:name (n6 / name :op1 "serine"~e.17)
:part-of (p5 / protein
:name (n3 / name :op1 "IRS-1"~e.13,15,20,22))))
:ARG1 (a3 / activity-06~e.28
:ARG0 (e / enzyme
:name (n5 / name :op1 "receptor"~e.25 :op2 "tyrosine"~e.26 :op3 "kinase"~e.27)
:mod (i6 / insulin~e.24)))
:ARG0-of (l / lead-03~e.31
:ARG2~e.32 (s2 / signal-07~e.35
:location (d / downstream~e.34)
:ARG1-of (i4 / impair-01~e.33)))))
# ::id bel_pmid_1019_4465.23770 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok other SH2 proteins , such as Crk ( adaptor ) , Nck ( adaptor ) , Fyn ( tyrosine kinase ) , and Csk ( tyrosine kinase ) , bind to tyrosine residues on IRS proteins through their specific SH2 domains .
# ::alignments 0-1.1.3 1-1.1.1.1 2-1.1 4-1.1.2.r 5-1.1.2.r 6-1.1.2.1.1.1 8-1.1.2.1.2.1 11-1.1.2.2.1.1 13-1.1.2.1.2.1 16-1.1.2.3.1.1 18-1.1.2.3.2.1.1.1 19-1.1.2.3.2.1.1.2 22-1.1.2 23-1.1.2.4.1.1 25-1.1.2.3.2.1.1.1 26-1.1.2.3.2.1.1.2 29-1 30-1.2.r 31-1.2.1.1.1 32-1.2 33-1.2.2.r 34-1.2.2.2.1.1 35-1.1.2.1 35-1.1.2.2 35-1.1.2.4 35-1.2.2 35-1.2.2.2 35-1.2.2.2.r 38-1.2.2.3 39-1.1.1.1 39-1.2.2.1.1 40-1.1.1.2 40-1.2.2.1.2
(b / bind-01~e.29
:ARG1 (p / protein-segment~e.2
:name (n / name :op1 "SH2"~e.1,39 :op2 "domain"~e.40)
:example~e.4,5 (a / and~e.22
:op1 (p2 / protein~e.35
:name (n2 / name :op1 "Crk"~e.6)
:ARG1-of (d / describe-01
:ARG2 (a2 / adaptor~e.8,13)))
:op2 (p3 / protein~e.35
:name (n3 / name :op1 "Nck"~e.11)
:ARG1-of (d2 / describe-01
:ARG2 a2))
:op3 (e2 / enzyme
:name (n4 / name :op1 "Fyn"~e.16)
:ARG1-of (d3 / describe-01
:ARG2 (e / enzyme
:name (n6 / name :op1 "tyrosine"~e.18,25 :op2 "kinase"~e.19,26))))
:op4 (p5 / protein~e.35
:name (n5 / name :op1 "Csk"~e.23)
:ARG1-of (d4 / describe-01
:ARG2 e)))
:mod (o / other~e.0))
:ARG2~e.30 (r / residue~e.32
:mod (a4 / amino-acid
:name (n7 / name :op1 "tyrosine"~e.31))
:part-of~e.33 (p7 / protein-segment~e.35
:name (n9 / name :op1 "SH2"~e.39 :op2 "domain"~e.40)
:part-of~e.35 (p6 / protein~e.35
:name (n8 / name :op1 "IRS"~e.34))
:ARG1-of (s / specific-02~e.38))))
# ::id bel_pmid_1019_4465.23772 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Fyn is not activated directly by the insulin receptor , but rather by interaction with IRS @-@ 1 ( 49 ) and another insulin receptor substrate , c @-@ Cbl ( 50 ) .
# ::alignments 0-1.1.3.1.1 2-1.1.1 2-1.1.1.r 3-1.1 3-1.2 4-1.1.4 5-1.1.2.r 7-1.1.2.1 8-1.1.2 10-1 11-1 12-1.2.1.r 13-1.2.1 14-1.2.1.2.r 15-1.2.1.2.1.1.1 17-1.2.1.2.1.1.1 19-1.2.1.2.1.2.1.1.1 21-1.2.1.2 22-1.2.1.2.2.4 23-1.2.1.2.2.1.1 24-1.2.1.2.2.1 25-1.2.1.2.2 27-1.2.1.2.2.3.1.1.1 29-1.2.1.2.2.3.1.1.1 31-1.2.1.2.2.2.1.1.1
(c3 / contrast-01~e.10,11
:ARG1 (a / activate-01~e.3 :polarity~e.2 -~e.2
:ARG0~e.5 (r / receptor~e.8
:mod (i / insulin~e.7))
:ARG1 (e / enzyme
:name (n2 / name :op1 "Fyn"~e.0))
:ARG1-of (d / direct-02~e.4))
:ARG2 (a2 / activate-01~e.3
:ARG0~e.12 (i2 / interact-01~e.13
:ARG0 e
:ARG1~e.14 (a3 / and~e.21
:op1 (p2 / protein
:name (n3 / name :op1 "IRS-1"~e.15,17)
:ARG1-of (d2 / describe-01
:ARG0 (p3 / publication
:ARG1-of (c / cite-01 :ARG2 49~e.19))))
:op2 (s / substrate~e.25
:mod (r2 / receptor~e.24
:mod i~e.23)
:ARG1-of (d3 / describe-01
:ARG0 (p4 / publication
:ARG1-of (c2 / cite-01 :ARG2 50~e.31)))
:ARG0-of (m / mean-01
:ARG1 (p5 / protein
:name (n / name :op1 "c-Cbl"~e.27,29)))
:mod (a4 / another~e.22))))
:ARG1 e))
# ::id bel_pmid_1019_4465.23788 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Recently , b1 integrins have also been reported to enhance IRS @-@ 1 phosphorylation and interaction , but not glucose transport , with downstream molecules such as PI3 @-@ kinase and Akt ( 74 ) . These results suggest that integrins and insulin @/@ IGF @-@ 1 receptor signaling pathways converge at an early point in the signaling cascade around the IRS proteins .
# ::alignments 0-1.1.2 2-1.1.1.1.1.1.1 3-1.1.1.1.1.1.2 5-1.1.4 7-1.1 9-1.1.1.1 9-1.1.1.2 10-1.1.1.1.2.1.1.1.1 12-1.1.1.1.2.1.1.1.1 13-1.1.1.1.2.1 14-1.1.1.1.2 15-1.1.1.1.2.2 17-1.1.1 18-1.1.1.2.1 18-1.1.1.2.1.r 19-1.1.1.2.2.1.1.1 20-1.1.1.2.2 22-1.1.1.2.3.r 23-1.1.1.2.3 24-1.1.1.2.3 25-1.1.1.2.3 26-1.1.1.2.3 27-1.1.1.2.3 28-1.1.1.2.3 29-1.1.1.2.3 30-1.1.1.2.3 31-1.1.1.2.3 33-1.1.3.1.1.1 36-1.2.1.2 37-1.2.1 37-1.2.1.1 37-1.2.1.1.r 38-1.2 39-1.2.2.r 40-1.2.2.1.1.1 42-1.2.2.2.1.1 44-1.2.2.2.1.1 46-1.2.2.2.1.1 47-1.2.2.2.1.2 47-1.2.2.2.2.1 48-1.2.2.2.2 49-1.2.2.2 50-1.2.2 51-1.2.2.3.r 53-1.2.2.3.1 54-1.2.2.3 55-1.2.2.3.2.r 57-1.2.2.3.2.1 58-1.2.2.3.2 59-1.2.2.3.2.2 61-1.2.2.3.2.2.1.1.1 62-1.1.1.1.1 62-1.1.1.1.2.1.1 62-1.2.2.1 62-1.2.2.3.2.2.1
(m / multi-sentence
:snt1 (r / report-01~e.7
:ARG1 (c / contrast-01~e.17
:ARG1 (e / enhance-01~e.9
:ARG0 (p12 / protein~e.62
:name (n / name :op1 "b1"~e.2 :op2 "integrin"~e.3))
:ARG1 (a / and~e.14
:op1 (p3 / phosphorylate-01~e.13
:ARG1 (p4 / protein~e.62
:name (n2 / name :op1 "IRS-1"~e.10,12)))
:op2 (i / interact-01~e.15
:ARG0 p4
:ARG1 (m2 / molecule
:mod (d / downstream)
:example (a2 / and
:op1 (e3 / enzyme
:name (n4 / name :op1 "PI3-kinase"))
:op2 (e5 / enzyme
:name (n5 / name :op1 "Akt")))))))
:ARG2 (e2 / enhance-01~e.9 :polarity~e.18 -~e.18
:ARG0 (t2 / transport-01~e.20
:ARG1 (s4 / small-molecule
:name (n3 / name :op1 "glucose"~e.19)))
:ARG1~e.22 a~e.23,24,25,26,27,28,29,30,31))
:time (r2 / recent~e.0)
:ARG1-of (d2 / describe-01
:ARG0 (p6 / publication
:ARG1-of (c2 / cite-01 :ARG2 74~e.33)))
:mod (a5 / also~e.5))
:snt2 (s / suggest-01~e.38
:ARG0 (t3 / thing~e.37
:ARG2-of~e.37 (r3 / result-01~e.37)
:mod (t / this~e.36))
:ARG1~e.39 (c3 / converge-01~e.50
:ARG0 (p10 / protein~e.62
:name (n8 / name :op1 "integrin"~e.40))
:ARG1 (p9 / pathway~e.49
:name (n6 / name :op1 "insulin/IGF-1"~e.42,44,46 :op2 "receptor"~e.47)
:ARG0-of (s3 / signal-07~e.48
:mod (r5 / receptor~e.47)))
:time~e.51 (p7 / point~e.54
:mod (e4 / early~e.53)
:subevent-of~e.55 (c4 / cascade~e.58
:subevent (s2 / signal-07~e.57)
:location (a4 / around~e.59
:op1 (p8 / protein~e.62
:name (n7 / name :op1 "IRS"~e.61))))))))
# ::id bel_pmid_1019_4465.24722 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok PC @-@ 1 is a membrane glycoprotein with ectonucleotide pyrophosphatase activity that seems to act as an intrinsic inhibitor of insulin receptor tyrosine kinase activity
# ::alignments 0-1.4.1.1 2-1.4.1.1 3-1.4.r 5-1.1 6-1 8-1.2.1.1.1.1 9-1.2.1.1.1.2 10-1.2.1 12-1.3.2 14-1.3 15-1.3.1.r 17-1.3.1.3 18-1.3.1 20-1.3.1.2.1.2 21-1.3.1.2.1.1.1 22-1.3.1.2.1.1.2 23-1.3.1.2.1.1.3 24-1.2.1 24-1.3.1.2
(g / glycoprotein~e.6
:mod (m / membrane~e.5)
:ARG0-of (h2 / have-03
:ARG1 (a / activity-06~e.10,24
:ARG0 (e / enzyme
:name (n3 / name :op1 "ectonucleotide"~e.8 :op2 "pyrophosphatase"~e.9))))
:ARG0-of (a2 / act-01~e.14
:ARG1~e.15 (i2 / inhibit-01~e.18
:ARG0 p2
:ARG1 (a3 / activity-06~e.24
:ARG0 (e2 / enzyme
:name (n4 / name :op1 "receptor"~e.21 :op2 "tyrosine"~e.22 :op3 "kinase"~e.23)
:mod (i / insulin~e.20)))
:mod (i3 / intrinsic~e.17))
:ARG1-of (s / seem-01~e.12))
:domain~e.3 (p2 / protein
:name (n2 / name :op1 "PC-1"~e.0,2)))
# ::id bel_pmid_1019_4465.24724 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok It has been reported that PC @-@ 1 overexpression in skeletal muscle of obese subjects explains downregulation of insulin receptor tyrosine phosphorylation
# ::alignments 3-1 4-1.1.r 5-1.1.1.1.1.1 7-1.1.1.1.1.1 8-1.1.1 9-1.1.1.2.r 10-1.1.1.2.1 11-1.1.1.2 12-1.1.1.2.2.r 13-1.1.1.2.2.1 14-1.1.1.2.2 15-1.1 16-1.1.2 17-1.1.2.1.r 18-1.1.2.1.1.1.1 19-1.1.2.1.1.1.2 20-1.1.2.1.1.1.3 21-1.1.2.1
(r / report-01~e.3
:ARG1~e.4 (e / explain-01~e.15
:ARG0 (o / overexpress-01~e.8
:ARG1 (p3 / protein
:name (n / name :op1 "PC-1"~e.5,7))
:location~e.9 (m / muscle~e.11
:mod (s / skeletal~e.10)
:part-of~e.12 (s2 / subject~e.14
:mod (o2 / obese~e.13))))
:ARG1 (d / downregulate-01~e.16
:ARG1~e.17 (p / phosphorylate-01~e.21
:ARG1 (p2 / protein
:name (n2 / name :op1 "insulin"~e.18 :op2 "receptor"~e.19 :op3 "tyrosine"~e.20))))))
# ::id bel_pmid_1022_8560.5928 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Inhibition of MEK1 also led to reduced expression of alpha @-@ enolase , phosphoglycerate kinase , elongation factor 2 and heterogeneous nuclear ribonucleoprotein A3 , the latter two being detected as truncated proteins .
# ::alignments 0-1.1 1-1.1.1.r 2-1.1.1.1.1 3-1.3 4-1 5-1.2.r 6-1.2.2 7-1.2 8-1.2.1.r 9-1.2.1.1.1.1 11-1.2.1.1.1.1 13-1.2.1.2.1.1 14-1.2.1.2.1.2 16-1.2.1.3.1.1 17-1.2.1.3.1.2 18-1.2.1.3.1.3 19-1.2.1 20-1.2.1.4.1.1 21-1.2.1.4.1.2 22-1.2.1.4.1.3 23-1.2.1.4.1.4 27-1.2.1.3.2.2.1 29-1.2.1.3.2 30-1.2.1.3.2.1.r 31-1.2.1.3.2.1.1 32-1.2.1.3.2.1
(l / lead-03~e.4
:ARG0 (i / inhibit-01~e.0
:ARG1~e.1 (e / enzyme
:name (n / name :op1 "MEK1"~e.2)))
:ARG2~e.5 (e2 / express-03~e.7
:ARG1~e.8 (a / and~e.19
:op1 (e3 / enzyme
:name (n2 / name :op1 "alpha-enolase"~e.9,11))
:op2 (e4 / enzyme
:name (n3 / name :op1 "phosphoglycerate"~e.13 :op2 "kinase"~e.14))
:op3 (p / protein
:name (n4 / name :op1 "elongation"~e.16 :op2 "factor"~e.17 :op3 2~e.18)
:ARG0-of (d / detect-01~e.29
:ARG1~e.30 (p3 / protein~e.32
:ARG1-of (t / truncate-01~e.31))
:ord (o / ordinal-entity :value -2~e.27)))
:op4 (p2 / protein
:name (n5 / name :op1 "heterogeneous"~e.20 :op2 "nuclear"~e.21 :op3 "ribonucleoprotein"~e.22 :op4 "A3"~e.23)
:ARG0-of d))
:ARG1-of (r / reduce-01~e.6))
:mod (a2 / also~e.3))
# ::id bel_pmid_1023_2608.5936 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In support of these data , we also show that MEK1 is highly phosphorylated in vivo on Ser 217 @/@ 221 in MLK3 @-@ transformed fibroblasts
# ::alignments 0-1.2.3 1-1.3 2-1.3.1.r 3-1.3.1.1 4-1.3.1 6-1.1 7-1.4 8-1 10-1.2.1.1.3.1.1 12-1.2.2 13-1.2 14-1.2.3 15-1.2.3 17-1.2.1.1.2.1 17-1.2.1.2.2.1 18-1.2.1.1.1 19-1.2.1 20-1.2.1.2.1 21-1.2.3 21-1.2.4.r 22-1.2.4.1.1.1.1 24-1.2.4.1 25-1.2.4
(s / show-01~e.8
:ARG0 (w / we~e.6)
:ARG1 (p / phosphorylate-01~e.13
:ARG1 (s2 / slash~e.19
:op1 (a / amino-acid :mod 217~e.18
:name (n2 / name :op1 "serine"~e.17)
:part-of (e / enzyme
:name (n5 / name :op1 "MEK1"~e.10)))
:op2 (a3 / amino-acid :mod 221~e.20
:name (n4 / name :op1 "serine"~e.17)
:part-of e))
:ARG1-of (h / high-02~e.12)
:manner (i / in-vivo~e.0,14,15,21)
:location~e.21 (f / fibroblast~e.25
:ARG1-of (t / transform-01~e.24
:ARG0 (e2 / enzyme
:name (n3 / name :op1 "MLK3"~e.22)))))
:purpose (s3 / support-01~e.1
:ARG1~e.2 (d / data~e.4
:mod (t2 / this~e.3)))
:mod (a2 / also~e.7))
# ::id bel_pmid_1023_2608.16572 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok expression of MLK3 strongly activated SAPK ? to the same extent seen with the established JNK @/@ SAPK activator arsenite ( 45 )
# ::alignments 0-1.1 1-1.1.1.r 2-1.1.1.1.1 3-1.3 4-1 5-1.2.1.1 9-1.4.2 10-1.4.r 11-1.4 12-1.4.1.r 14-1.4.1.2 15-1.4.1.1.1.1.1 17-1.4.1.1.1.1.1 18-1.4.1.1 19-1.4.1 21-1.5.1.1.1
(a / activate-01~e.4
:ARG0 (e / express-03~e.0
:ARG2~e.1 (e2 / enzyme
:name (n / name :op1 "MLK3"~e.2)))
:ARG1 (e4 / enzyme
:name (n2 / name :op1 "SAPK"~e.5))
:ARG1-of (s / strong-02~e.3)
:extent~e.10 (s2 / see-01~e.11
:ARG1~e.12 (a2 / arsenite~e.19
:ARG0-of (a3 / activate-01~e.18
:ARG1 (p2 / pathway
:name (n3 / name :op1 "JNK/SAPK"~e.15,17)))
:ARG1-of (e3 / establish-01~e.14))
:ARG1-of (s3 / same-01~e.9))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c / cite-01 :ARG2 45~e.21))))
# ::id bel_pmid_1023_2608.23890 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Using a coupled assay , we were able to show that MLK3 @-@ mediated phosphorylation of SEK1 resulted in activation because GST @-@ SEK1 is able to phosphorylate recombinant SAPK ? ( Fig . 5D )
# ::alignments 0-1.2 2-1.2.2.1 3-1.2.2 5-1.1.1 7-1 9-1.1 10-1.1.2.r 11-1.1.2.1.2.1.1.1 13-1.1.2.1.2 14-1.1.2.1 15-1.1.2.1.1.r 16-1.1.2.1.1.1.1 17-1.1.2 18-1.1.2.2.r 19-1.1.2.2 20-1.1.2.3 21-1.1.2.3.1.1.2.1.1 23-1.1.2.3.1.1.2.1.1 25-1.1.2.3.1 27-1.1.2.3.1.1 28-1.1.2.3.1.1.1.2 29-1.1.2.3.1.1.1.1.1 32-1.3.1 34-1.3.1.1
(p / possible-01~e.7
:ARG1 (s / show-01~e.9
:ARG0 (w / we~e.5)
:ARG1~e.10 (r / result-01~e.17
:ARG1 (p3 / phosphorylate-01~e.14
:ARG1~e.15 (e3 / enzyme
:name (n / name :op1 "SEK1"~e.16))
:ARG1-of (m / mediate-01~e.13
:ARG0 (e / enzyme
:name (n2 / name :op1 "MLK3"~e.11))))
:ARG2~e.18 (a / activate-01~e.19)
:ARG1-of (c / cause-01~e.20
:ARG0 (p5 / possible-01~e.25
:ARG1 (p2 / phosphorylate-01~e.27
:ARG1 (e2 / enzyme
:name (n3 / name :op1 "SAPK"~e.29)
:ARG3-of (r2 / recombine-01~e.28))
:ARG2 (p7 / protein
:name (n4 / name :op1 "GST-SEK1"~e.21,23)))))))
:manner (u / use-01~e.0
:ARG0 w
:ARG1 (a2 / assay-01~e.3
:ARG1-of (c2 / couple-01~e.2)))
:ARG1-of (d / describe-01
:ARG2 (f / figure~e.32 :mod "5D"~e.34)))
# ::id bel_pmid_1023_2608.23894 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Wild type , but not KD , MLK3 was able to phosphorylate His @-@ MEK1 ( Fig . 5A ) ? and GST @-@ SEK1 ( Fig . 5B ) ? in vitro .
# ::alignments 0-1.1.1.2.2 1-1.1.1.2.2 3-1 4-1.2.1 4-1.2.1.r 4-1.2.2.2.2.1 4-1.2.2.2.2.1.r 7-1.1.1.2.1.1 7-1.2.2.2.1.1 9-1.1 9-1.2 11-1.1.1 11-1.2.2 12-1.1.1.1.1.1.1 14-1.1.1.1.1.1.2 16-1.1.1.1.1.2.1 18-1.1.1.1.1.2.1.1 21-1.1.1.1 22-1.1.1.1.2.1.1 24-1.1.1.1.2.1.1 26-1.1.1.1.2.2.1 28-1.1.1.1.2.2.1.1 31-1.1.1.3 32-1.1.1.3
(c / contrast-01~e.3
:ARG1 (p / possible-01~e.9
:ARG1 (p2 / phosphorylate-01~e.11
:ARG1 (a2 / and~e.21
:op1 (p3 / protein
:name (n / name :op1 "His"~e.12 :op2 "MEK1"~e.14)
:ARG1-of (d / describe-01
:ARG2 (f / figure~e.16 :mod "5A"~e.18)))
:op2 (p4 / protein
:name (n2 / name :op1 "GST-SEK1"~e.22,24)
:ARG1-of (d2 / describe-01
:ARG2 (f2 / figure~e.26 :mod "5B"~e.28))))
:ARG2 (e / enzyme
:name (n3 / name :op1 "MLK3"~e.7)
:mod (w / wild-type~e.0,1))
:manner (i / in-vitro~e.31,32)))
:ARG2 (p5 / possible-01~e.9 :polarity~e.4 -~e.4
:ARG1 (p6 / phosphorylate-01~e.11
:ARG1 a2
:ARG2 (e2 / enzyme
:name (n5 / name :op1 "MLK3"~e.7)
:ARG0-of (f3 / function-01 :polarity~e.4 -~e.4
:ARG1 (k / kinase))))))
# ::id bel_pmid_1034_3541.46 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Thrombin receptor mediated signal transduction could induce the expressions of IL6 and G @-@ CSF , and increase inflammatory events in the cavum articulare via NF @-@ kappa B activation
# ::alignments 0-1.1.1.1.2.1.1.1 1-1.1.1.1.2.1 2-1.1.1.1.2 3-1.1.1.1.1 4-1.1.1.1 5-1 6-1.1.1 8-1.1.1.2 9-1.1.1.2.1.r 10-1.1.1.2.1.1.1.1 11-1.1.1.2.1 12-1.1.1.2.1.2.1.1 14-1.1.1.2.1.2.1.1 16-1.1 17-1.1.2 18-1.1.2.2.1 19-1.1.2.2 20-1.1.2.3.r 22-1.1.2.3 23-1.1.2.3.1 25-1.1.2.4.1.1.1 27-1.1.2.4.1.1.1 28-1.1.2.4.1.1.1 29-1.1.2.4
(p / possible-01~e.5
:ARG1 (a / and~e.16
:op1 (i / induce-01~e.6
:ARG0 (t / transduce-01~e.4
:ARG1 (s / signal-07~e.3)
:ARG1-of (m / mediate-01~e.2
:ARG0 (r / receptor~e.1
:name (n / name :op1 "thrombin"~e.0))))
:ARG2 (e / express-03~e.8
:ARG2~e.9 (a2 / and~e.11
:op1 (p2 / protein
:name (n2 / name :op1 "IL6"~e.10))
:op2 (p3 / protein
:name (n3 / name :op1 "G-CSF"~e.12,14)))))
:op2 (i2 / increase-01~e.17
:ARG0 t
:ARG1 (e2 / event~e.19
:mod (i3 / inflame-01~e.18))
:location~e.20 (c / cavum~e.22
:mod (a3 / articulare~e.23))
:manner (a4 / activate-01~e.29
:ARG1 (p4 / protein
:name (n4 / name :op1 "NF-kappa-B"~e.25,27,28))))))
# ::id bel_pmid_1034_3541.18504 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Thrombin receptor mediated signal transduction could induce the expressions of IL6 and G @-@ CSF , and increase inflammatory events in the cavum articulare via NF-êB activation
# ::alignments 0-1.1.1.1.2.1.1.1 1-1.1.1.1.2.1 2-1.1.1.1.2 3-1.1.1.1.1 4-1.1.1.1 5-1 6-1.1.1 8-1.1.1.2 9-1.1.1.2.1.r 10-1.1.1.2.1.1.1.1 11-1.1.1.2.1 12-1.1.1.2.1.2.1.1 14-1.1.1.2.1.2.1.1 16-1.1 17-1.1.2 18-1.1.2.2.1 19-1.1.2.2 20-1.1.2.3.r 22-1.1.2.3 23-1.1.2.3.1 26-1.1.2.4
(p / possible-01~e.5
:ARG1 (a / and~e.16
:op1 (i / induce-01~e.6
:ARG0 (t / transduce-01~e.4
:ARG1 (s / signal-07~e.3)
:ARG1-of (m / mediate-01~e.2
:ARG0 (r / receptor~e.1
:name (n / name :op1 "thrombin"~e.0))))
:ARG2 (e / express-03~e.8
:ARG2~e.9 (a2 / and~e.11
:op1 (p2 / protein
:name (n2 / name :op1 "IL6"~e.10))
:op2 (p3 / protein
:name (n3 / name :op1 "G-CSF"~e.12,14)))))
:op2 (i2 / increase-01~e.17
:ARG0 t
:ARG1 (e2 / event~e.19
:mod (i3 / inflame-01~e.18))
:location~e.20 (c / cavum~e.22
:mod (a3 / articulare~e.23))
:manner (a4 / activate-01~e.26
:ARG1 (p4 / protein
:name (n4 / name :op1 "NF-κB"))))))
# ::id bel_pmid_1034_3541.23056 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The levels of IL6 and of G @-@ CSF mRNAs showed a time dependent increase during two to eight hours after thrombin stimulation .... Cytokines were measured by enzyme linked immunosorbent assay ( ELISA ) in the supernatants of cultured rheumatoid synovial fibroblasts stimulated by thrombin
# ::alignments 1-1.1.1.1 1-1.1.1.2 2-1.1.1.1.1.r 3-1.1.1.1.1.2.1.1.1 4-1.1.1 5-1.1.1.2.1.r 6-1.1.1.2.1.2.1.1.1 8-1.1.1.2.1.2.1.1.1 9-1.1.1.1.1.1.1 9-1.1.1.2.1.1.1 10-1.1 12-1.1.2.1.1 12-1.1.2.2.2.1 12-1.1.2.2.2.2 13-1.1.2.1 14-1.1.2 15-1.1.2.2.r 16-1.1.2.2.2.1.1 18-1.1.2.2.2.2.1 19-1.1.2.2.2.1.2 20-1.1.2.2 21-1.1.2.2.1.1.1.1 22-1.1.2.2.1 24-1.2.1.1.1 26-1.2 27-1.2.3.r 28-1.2.3.1.1.1 29-1.2.3.1.1 30-1.2.3.1 31-1.2.3 35-1.2.2.r 37-1.2.2 38-1.2.2.1.r 39-1.2.2.1 40-1.2.2.1.1.2 41-1.2.2.1.1.1 42-1.2.2.1.1 43-1.2.2.2 44-1.2.2.2.1.r 45-1.2.2.2.1
(m / multi-sentence
:snt1 (s / show-01~e.10
:ARG0 (a / and~e.4
:op1 (l / level~e.1
:quant-of~e.2 (n9 / nucleic-acid
:name (n / name :op1 "mRNA"~e.9)
:ARG0-of (e4 / encode-01
:ARG1 (p3 / protein
:name (n2 / name :op1 "IL6"~e.3)))))
:op2 (l2 / level~e.1
:quant-of~e.5 (n10 / nucleic-acid
:name (n3 / name :op1 "mRNA"~e.9)
:ARG0-of (e3 / encode-01
:ARG1 (p2 / protein
:name (n4 / name :op1 "G-CSF"~e.6,8))))))
:ARG1 (i / increase-01~e.14
:ARG0-of (d / depend-01~e.13
:ARG1 (t / time~e.12))
:time~e.15 (a2 / after~e.20
:op1 (s2 / stimulate-01~e.22
:ARG1 (e / enzyme
:name (n5 / name :op1 "thrombin"~e.21)))
:quant (b / between
:op1 (t2 / temporal-quantity~e.12 :quant 2~e.16
:unit (h / hour~e.19))
:op2 (t3 / temporal-quantity~e.12 :quant 8~e.18
:unit h)))))
:snt2 (m2 / measure-01~e.26
:ARG1 (p / protein
:name (n8 / name :op1 "cytokine"~e.24))
:location~e.35 (s3 / supernatant~e.37
:part-of~e.38 (c2 / culture-01~e.39
:ARG1 (f / fibroblast~e.42
:location (s4 / synovia~e.41)
:mod (r3 / rheumatoid~e.40)))
:ARG1-of (s5 / stimulate-01~e.43
:ARG0~e.44 e~e.45))
:manner~e.27 (a3 / assay-01~e.31
:instrument (i2 / immunosorbent~e.30
:ARG1-of (l3 / link-01~e.29
:ARG2 (e2 / enzyme~e.28))))))
# ::id bel_pmid_1034_3541.35586 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Thrombin receptor mediated signal transduction could induce the expressions of IL6 and G @-@ CSF , and increase inflammatory events in the cavum articulare via NF-êB activation
# ::alignments 0-1.1.1.1.2.1.1.1 1-1.1.1.1.2.1 2-1.1.1.1.2 3-1.1.1.1.1 4-1.1.1.1 5-1 6-1.1.1 8-1.1.1.2 9-1.1.1.2.1.r 10-1.1.1.2.1.1.1.1 11-1.1.1.2.1 12-1.1.1.2.1.2.1.1 14-1.1.1.2.1.2.1.1 16-1.1 17-1.1.2 18-1.1.2.2.1 19-1.1.2.2 20-1.1.2.3.r 22-1.1.2.3 23-1.1.2.3.1 26-1.1.2.4
(p / possible-01~e.5
:ARG1 (a / and~e.16
:op1 (i / induce-01~e.6
:ARG0 (t / transduce-01~e.4
:ARG1 (s / signal-07~e.3)
:ARG1-of (m / mediate-01~e.2
:ARG0 (r / receptor~e.1
:name (n / name :op1 "thrombin"~e.0))))
:ARG2 (e / express-03~e.8
:ARG2~e.9 (a2 / and~e.11
:op1 (p2 / protein
:name (n2 / name :op1 "IL6"~e.10))
:op2 (p3 / protein
:name (n3 / name :op1 "G-CSF"~e.12,14)))))
:op2 (i2 / increase-01~e.17
:ARG0 t
:ARG1 (e2 / event~e.19
:mod (i3 / inflame-01~e.18))
:location~e.20 (c / cavum~e.22
:mod (a3 / articulare~e.23))
:manner (a4 / activate-01~e.26
:ARG1 (p4 / protein
:name (n4 / name :op1 "NF-κB"))))))
# ::id bel_pmid_1034_7197.8888 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Induction of the urokinase promoter by HGF @/@ SF via the Met receptor was blocked by co @-@ expression of a dominant @-@ negative Grb2 and Sos1 expression construct .
# ::alignments 0-1.2 1-1.2.2.r 3-1.2.2.1.1.1.1 4-1.2.2 4-1.2.2.1 4-1.2.2.1.r 5-1.2.1.r 6-1.2.1.1.1 8-1.2.1.1.1 11-1.2.3.1.1 12-1.2.3 14-1 18-1.1.1.1.2 21-1.1.1.1.1 21-1.1.1.1.1.3 21-1.1.1.1.1.3.r 24-1.1.1.1.1.1.1 25-1.1.1.1 26-1.1.1.1.2.1.1.1 27-1.1.1.1.2 28-1.1.1
(b / block-01~e.14
:ARG0 (c / coexpress-01
:ARG2 (c2 / construct-01~e.28
:ARG1 (a / and~e.25
:op1 (p / protein~e.21
:name (n / name :op1 "Grb2"~e.24)
:ARG2-of (m / mutate-01 :mod "-/-")
:ARG0-of~e.21 (d / dominate-01~e.21))
:op2 (e / express-03~e.18,27
:ARG2 (p2 / protein
:name (n2 / name :op1 "Sos1"~e.26))))))
:ARG1 (i / induce-01~e.0
:ARG0~e.5 (p3 / protein
:name (n3 / name :op1 "HGF/SF"~e.6,8))
:ARG2~e.1 (m2 / molecular-physical-entity~e.4
:ARG0-of~e.4 (p4 / promote-01~e.4
:ARG1 (e2 / enzyme
:name (n4 / name :op1 "urokinase"~e.3))))
:medium (r / receptor~e.12
:name (n5 / name :op1 "Met"~e.11))))
# ::id bel_pmid_1034_7197.20912 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Further , the expression of the catalytically inactive mutants of Ha @-@ Ras , RhoA , c @-@ Raf , and Erk2 or addition of the Mek1 @-@ specific inhibitor PD 098059 abrogated the stimulation of the urokinase promoter by HGF/SF .
# ::alignments 3-1.1.2.1 7-1.1.2.1.1.2.1 8-1.1.2.1.1 9-1.1.2.1.1.1.r 10-1.1.2.1.1.1.1.1.1 12-1.1.2.1.1.1.1.1.1 14-1.1.2.1.1.1.2.1.1 16-1.1.2.1.1.1.3.1.1 18-1.1.2.1.1.1.3.1.1 20-1.1.2.1.1.1 21-1.1.2.1.1.1.4.1.1 22-1.1.2 23-1.1.2.2 24-1.1.2.2.1.r 26-1.1.2.2.1.2.1.1.1.1 28-1.1.2.2.1.2.1 29-1.1.2.2.1 29-1.1.2.2.1.2 29-1.1.2.2.1.2.r 30-1.1.2.2.1.1.1 31-1.1.2.2.1.1.1 32-1.1 34-1.1.1 35-1.1.1.2.r 37-1.1.1.2.1.1.1.1 38-1.1.1.2 38-1.1.1.2.1 38-1.1.1.2.1.r 39-1.1.1.1.r 40-1.1.1.1.1.1
(a / and
:op2 (a2 / abrogate-01~e.32
:ARG1 (s / stimulate-01~e.34
:ARG0~e.39 (p / protein
:name (n / name :op1 "HGF/SF"~e.40))
:ARG1~e.35 (m / molecular-physical-entity~e.38
:ARG0-of~e.38 (p2 / promote-01~e.38
:ARG1 (e / enzyme
:name (n2 / name :op1 "urokinase"~e.37)))))
:ARG2 (o / or~e.22
:op1 (e2 / express-03~e.3
:ARG2 (m2 / mutate-01~e.8
:ARG1~e.9 (a3 / and~e.20
:op1 (e6 / enzyme
:name (n3 / name :op1 "Ha-Ras"~e.10,12))
:op2 (p4 / protein
:name (n4 / name :op1 "RhoA"~e.14))
:op3 (e3 / enzyme
:name (n5 / name :op1 "c-Raf"~e.16,18))
:op3 (e4 / enzyme
:name (n6 / name :op1 "Erk2"~e.21)))
:ARG1-of (a4 / activate-01 :polarity -~e.7
:manner (c / catalytic))))
:op2 (a5 / add-02~e.23
:ARG1~e.24 (m3 / molecular-physical-entity~e.29
:name (n7 / name :op1 "PD-098059"~e.30,31)
:ARG0-of~e.29 (i / inhibit-01~e.29
:ARG1-of (s2 / specific-02~e.28
:ARG2 (e5 / enzyme
:name (n8 / name :op1 "Mek1"~e.26)))))))))
# ::id bel_pmid_1035_9574.24516 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok c @-@ Raf @-@ 1 kinase was identified as an intracellular target of a signal transduction cascade initiated by binding of TNF @-@ alpha to TNFR @-@ I .
# ::alignments 0-1.1.1.1 2-1.1.1.1 4-1.1.1.1 5-1.1.1.2 7-1 8-1.2.r 10-1.2.3 11-1.2 12-1.2.1.r 14-1.2.1.1.1 15-1.2.1.1 16-1.2.1 17-1.2.1.2 18-1.2.1.2.1.r 19-1.2.1.2.1 20-1.2.1.2.1.1.r 21-1.2.1.2.1.1.1.1 23-1.2.1.2.1.1.1.1 24-1.2.1.2.1.2.r 25-1.2.1.2.1.2.1.1 27-1.2.1.2.1.2.1.1
(i / identify-01~e.7
:ARG1 (e / enzyme
:name (n / name :op1 "c-Raf-1"~e.0,2,4 :op2 "kinase"~e.5))
:ARG2~e.8 (t / target-01~e.11
:ARG0~e.12 (c / cascade-01~e.16
:ARG2-of (t2 / transduce-01~e.15
:ARG1 (s / signal-07~e.14))
:ARG1-of (i2 / initiate-01~e.17
:ARG2~e.18 (b / bind-01~e.19
:ARG1~e.20 (p / protein
:name (n2 / name :op1 "TNF-alpha"~e.21,23))
:ARG2~e.24 (p2 / protein
:name (n3 / name :op1 "TNFR-I"~e.25,27)))))
:ARG1 e
:location (i3 / intracellular~e.10)))
# ::id bel_pmid_1036_2260.5288 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Gadd45 was also able to physically interact with Cdc2 , but not Cyclin B1 . Addition of Gadd45 to immunoprecipitated Cdc2 @/@ Cyclin B1 in vitro led to a dissociation of this complex , and thus may represent a new checkpoint mechanism whereby Cdc2 @/@ Cyclin B1 can be inhibited .
# ::alignments 0-1.2.1.1.1.1 2-1.1.1.2 3-1.1.1 3-1.1.2 5-1.1.1.1.3 5-1.1.1.1.3.r 6-1.1.1.1 6-1.1.2.1 7-1.1.1.1.2.r 7-1.2.3.1.1.1.3.r 8-1.1.1.1.2.1.1 10-1.1 11-1.1.2.1.1 11-1.1.2.1.1.r 12-1.1.2.1.3.1.1 13-1.1.2.1.3.1.1 15-1.2.1 17-1.1.1.1.1.1.1 17-1.2.1.1.1.1 18-1.2.1.2.r 19-1.2.1.2.3 20-1.2.1.2.1.1.1 22-1.2.1.2.2.1.1 23-1.2.1.2.2.1.1 24-1.2.1.3 25-1.2.1.3 26-1.2 27-1.2.2.r 27-1.2.3 29-1.2.2 31-1.2.2.2.1 32-1.2.1.2 32-1.2.2.2 35-1.2.3 36-1.2.3.1 37-1.2.3.1.1 39-1.2.3.1.1.1.2 40-1.2.3.1.1.1.1 41-1.2.3.1.1.1 43-1.2.1.2.1.1.1 45-1.2.1.2.2.1.1 46-1.2.1.2.2.1.1 47-1.2.3.1.1.1.3 49-1.2.3.1.1.1.3.1
(m / multi-sentence
:snt1 (c / contrast-01~e.10
:ARG1 (p / possible-01~e.3
:ARG1 (i / interact-01~e.6
:ARG0 (p2 / protein
:name (n / name :op1 "Gadd45"~e.17))
:ARG1~e.7 (e2 / enzyme
:name (n2 / name :op1 "Cdc2"~e.8))
:manner~e.5 (p3 / physical~e.5))
:mod (a / also~e.2))
:ARG2 (p4 / possible-01~e.3
:ARG1 (i2 / interact-01~e.6 :polarity~e.11 -~e.11
:ARG0 p2
:ARG1 (p5 / protein
:name (n3 / name :op1 "Cyclin-B1"~e.12,13))
:ARG2 p3)))
:snt2 (l / lead-03~e.26
:ARG0 (a2 / add-02~e.15
:ARG1 (p6 / protein
:name (n4 / name :op1 "Gadd45"~e.0,17))
:ARG2~e.18 (m3 / macro-molecular-complex~e.32
:part (e / enzyme
:name (n5 / name :op1 "Cdc2"~e.20,43))
:part (p7 / protein
:name (n6 / name :op1 "Cyclin-B1"~e.22,23,45,46))
:ARG1-of (i3 / immunoprecipitate-01~e.19))
:manner (i4 / in-vitro~e.24,25))
:ARG2~e.27 (d / dissociate-01~e.29
:ARG0 a2
:ARG1 (c2 / complex~e.32
:mod (t / this~e.31)))
:ARG0-of (c3 / cause-01~e.27,35
:ARG1 (p8 / possible-01~e.36
:ARG1 (r / represent-01~e.37
:ARG0 (m5 / mechanism~e.41
:mod (c4 / checkpoint~e.40)
:ARG1-of (n7 / new-01~e.39)
:instrument-of~e.7 (p9 / possible-01~e.47
:ARG1 (i5 / inhibit-01~e.49
:ARG1 m3)))
:ARG1 a2)))))
# ::id bel_pmid_1036_2713.15636 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Treatment with TNF @-@ a significantly decreased the intracellular GSH content of HS @-@ 24 cells . Pretreatment of this culture with DMSO recovered the TNF @-@ a @-@ induced decrease in GSH ( Table 1 ) .
# ::alignments 0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.1.1 5-1.1.3 6-1.1 8-1.1.2.2.2 9-1.1.2.1.1 10-1.1.2 10-1.1.2.2 10-1.1.2.2.r 11-1.1.2.2.1.r 12-1.1.2.2.1.1.1 14-1.1.2.2.1.1.1 15-1.1.2.2.1 17-1.2.1 18-1.2.1.1.r 19-1.2.1.1.1 20-1.2.1.1 21-1.2.1.2.r 22-1.2.1.2.1.1 23-1.2 25-1.2.2.2.1.1.1 29-1.2.2.2 30-1.2.2 31-1.2.2.1.r 32-1.2.2.1.1.1 34-1.2.3.1 35-1.2.3.1.1
(m / multi-sentence
:snt1 (d / decrease-01~e.6
:ARG0 (t / treat-04~e.0
:ARG2~e.1 (p / protein
:name (n / name :op1 "TNF-α"~e.2)))
:ARG1 (s3 / small-molecule~e.10
:name (n2 / name :op1 "GSH"~e.9)
:ARG1-of~e.10 (c / contain-01~e.10
:ARG0~e.11 (c2 / cell~e.15
:name (n3 / name :op1 "HS-24"~e.12,14))
:location (i / intracellular~e.8)))
:ARG2 (s / significant-02~e.5))
:snt2 (r / recover-02~e.23
:ARG0 (p2 / pretreat-01~e.17
:ARG1~e.18 (c3 / culture~e.20
:mod (t2 / this~e.19))
:ARG3~e.21 (s2 / small-molecule
:name (n4 / name :op1 "DMSO"~e.22)))
:ARG1 (d2 / decrease-01~e.30
:ARG1~e.31 (s4 / small-molecule
:name (n5 / name :op1 "GSH"~e.32))
:ARG2-of (i2 / induce-01~e.29
:ARG0 (p3 / protein
:name (n6 / name :op1 "TNF-α"~e.25))))
:ARG1-of (d3 / describe-01
:ARG0 (t3 / table~e.34 :mod 1~e.35))))
# ::id bel_pmid_1036_2713.15640 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok TNF @-@ a ( 200 U/ml ) significantly increased the levels of IL @-@ 6 mRNA in HS @-@ 24 cells and DMSO ( 1.0 %) markedly reduced those induced with the cytokine ( Fig . 5E ) .
# ::alignments 0-1.1.1.1.1 4-1.1.1.2.1 7-1.1.3 8-1.1 10-1.1.2 10-1.2.2 11-1.1.2.1.r 12-1.1.2.1.2.1.1.1 14-1.1.2.1.2.1.1.1 15-1.1.2.1.1.1 16-1.1.4.r 17-1.1.4.1.1 19-1.1.4.1.1 20-1.1.4 21-1 22-1.2.1.1.1 24-1.2.1.2.1 26-1.2.3 26-1.2.3.r 27-1.2 29-1.2.2.1 30-1.2.2.1.1.r 32-1.2.2.1.1.1.1 34-1.3.1 36-1.3.1.1
(a / and~e.21
:op1 (i / increase-01~e.8
:ARG0 (p / protein
:name (n / name :op1 "TNF-α"~e.0)
:quant (c / concentration-quantity :quant 200~e.4
:unit (u / unit-per-milliliter)))
:ARG1 (l / level~e.10
:quant-of~e.11 (n7 / nucleic-acid
:name (n2 / name :op1 "mRNA"~e.15)
:ARG0-of (e / encode-01
:ARG1 (p4 / protein
:name (n5 / name :op1 "IL-6"~e.12,14)))))
:ARG2 (s / significant-02~e.7)
:location~e.16 (c2 / cell~e.20
:name (n3 / name :op1 "HS-24"~e.17,19)))
:op2 (r2 / reduce-01~e.27
:ARG0 (s2 / small-molecule
:name (n4 / name :op1 "DMSO"~e.22)
:quant (p2 / percentage-entity :quant 1.0~e.24))
:ARG1 (l2 / level~e.10
:ARG2-of (i2 / induce-01~e.29
:ARG0~e.30 (p3 / protein
:name (n6 / name :op1 "cytokine"~e.32)))
:quant-of n7)
:manner~e.26 (m2 / marked~e.26))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.34 :mod "5E"~e.36)))
# ::id bel_pmid_1036_2713.18726 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok An XO enzyme activity of 5.0 mU @/@ ml led to a twofold increase in IL @-@ 6 secretion in NHBE cells . And incubation of HS @-@ 24 cells with XO ( 20 mU/ml ) induced a 1.8 @-@ fold increase in IL @-@ 6 production
# ::alignments 1-1.2.1.1.2.1.1 2-1.1.1.1 2-1.1.2.2.1 2-1.2.1.1.2 2-1.2.1.2.2.1 3-1.1.1 4-1.1.1.1.2.r 5-1.1.1.1.2.1 8-1.1.1.1.2.2 8-1.2.1.1.2.2.2 9-1.1 13-1.1.2 14-1.1.2.2.r 15-1.1.2.2.1.1.1 17-1.1.2.2.1.1.1 18-1.1.2.2 19-1.1.2.4.r 20-1.1.2.4.1.1 21-1.1.2.4 23-1.2 24-1.2.1.1 25-1.2.1.1.1.r 26-1.2.1.1.1.1.1 28-1.2.1.1.1.1.1 29-1.2.1.1.1 31-1.1.1.1.1.1 31-1.2.1.1.2.1.1 33-1.2.1.1.2.2.1 36-1.2.1 38-1.2.1.2.3.1 40-1.2.1.2.3 41-1.2.1.2 42-1.2.1.2.2.r 43-1.2.1.2.2.1.1.1 45-1.2.1.2.2.1.1.1 46-1.2.1.2.2
(m / multi-sentence
:snt1 (l / lead-03~e.9
:ARG0 (a / activity-06~e.3
:ARG0 (e / enzyme~e.2
:name (n / name :op1 "XO"~e.31)
:quant~e.4 (c / concentration-quantity :quant 5.0~e.5
:unit (m2 / milliunit-per-milliliter~e.8))))
:ARG2 (i / increase-01~e.13
:ARG0 a
:ARG1~e.14 (s / secrete-01~e.18
:ARG1 (p / protein~e.2
:name (n2 / name :op1 "IL-6"~e.15,17)))
:ARG2 (p2 / product-of :op1 2)
:location~e.19 (c2 / cell~e.21
:name (n3 / name :op1 "NHBE"~e.20))))
:snt2 (a2 / and~e.23
:op2 (i2 / induce-01~e.36
:ARG0 (i3 / incubate-01~e.24
:ARG1~e.25 (c3 / cell~e.29
:name (n4 / name :op1 "HS-24"~e.26,28))
:ARG2 (e2 / enzyme~e.2
:name (n5 / name :op1 "XO"~e.1,31)
:quant (c4 / concentration-quantity :quant 20~e.33
:unit (m3 / milliunit-per-milliliter~e.8))))
:ARG2 (i4 / increase-01~e.41
:ARG0 i3
:ARG1~e.42 (p3 / produce-01~e.46
:ARG1 (p4 / protein~e.2
:name (n6 / name :op1 "IL-6"~e.43,45)))
:ARG2 (p5 / product-of~e.40 :op1 1.8~e.38)))))
# ::id bel_pmid_1036_2713.24360 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok SOD ( 250 U/ml ) significantly suppressed the IL @-@ 6 production and IL @-@ 6 mRNA expression induced by XO , whereas catalase ( 500 U/ml ) did not modulate the IL @-@ 6 response to XO ( Fig . 4 ) .
# ::alignments 0-1.1.1.1.1 2-1.1.1.2.1 5-1.1.3 6-1.1 8-1.1.2.1.1.1.1 10-1.1.2.1.1.1.1 11-1.1.2.1 13-1.1.2.1.1.1.1 15-1.1.2.1.1.1.1 16-1.1.2.2.1.1.1 17-1.1.2.2 18-1.1.2.3 19-1.1.2.3.1.r 20-1.1.2.3.1.1.1 22-1 23-1.2.2.1.1 25-1.2.2.2.1 29-1.2.1 29-1.2.1.r 30-1.2 32-1.2.3.1 33-1.2.3.1 34-1.2.3.1 35-1.2.3 36-1.2.3.2.r 37-1.2.3.2 39-1.3.1 41-1.3.1.1
(c / contrast-01~e.22
:ARG1 (s / suppress-01~e.6
:ARG0 (e / enzyme
:name (n / name :op1 "SOD"~e.0)
:quant (c2 / concentration-quantity :quant 250~e.2
:unit (u / unit-per-milliliter)))
:ARG1 (a / and
:op1 (p / produce-01~e.11
:ARG1 (p2 / protein
:name (n2 / name :op1 "IL-6"~e.8,10,13,15)))
:op2 (e2 / express-03~e.17
:ARG1 (n5 / nucleic-acid
:name (n3 / name :op1 "mRNA"~e.16)
:ARG0-of (e5 / encode-01
:ARG1 p2)))
:ARG2-of (i / induce-01~e.18
:ARG0~e.19 (e3 / enzyme
:name (n4 / name :op1 "XO"~e.20))))
:ARG1-of (s2 / significant-02~e.5))
:ARG2 (m / modulate-01~e.30 :polarity~e.29 -~e.29
:ARG0 (e4 / enzyme
:name (n6 / name :op1 "catalase"~e.23)
:quant (c3 / concentration-quantity :quant 500~e.25
:unit u))
:ARG1 (r2 / respond-01~e.35
:ARG0 p2~e.32,33,34
:ARG1~e.36 e3~e.37))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.39 :mod 4~e.41)))
# ::id bel_pmid_1036_2713.24536 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok TNF @-@ a significantly increased the production of IL @-@ 6 in WI @-@ 38 @-@ 40 cells . However , DMSO was not able to inhibit the TNF @-@ a @-@ induced IL @-@ 6 enhancement in both protein and mRNA levels ( Fig . 7 ) . These results suggest that ROIs may not be involved in the production of IL @-@ 6 in human lung fibroblasts
# ::alignments 0-1.1.1.1.1 3-1.1.3 4-1.1 6-1.1.2 7-1.1.2.1.r 8-1.1.2.1.1.1 10-1.1.2.1.1.1 11-1.1.4.r 12-1.1.4.1.1 14-1.1.4.1.1 16-1.1.4.1.1 17-1.1.4 19-1.2 21-1.2.1.2.1.1.1 23-1.2.1.1 23-1.2.1.1.r 24-1.2.1 26-1.2.1.2 28-1.2.1.2.2.2.1.1.1 32-1.2.1.2.2.2 33-1.2.1.2.2.1.1.1 35-1.2.1.2.2.1.1.1 36-1.2.1.2.2 39-1.2.1.2.2.3.1.1 40-1.2.1.2.2.3 41-1.2.1.2.2.3.2.1.1.1 42-1.2.1.2.2.3.1 42-1.2.1.2.2.3.2 44-1.2.2.1 46-1.2.2.1.1 49-1.3.1.2 50-1.3.1 50-1.3.1.1 50-1.3.1.1.r 51-1.3 54-1.3.2 55-1.3.2.1 55-1.3.2.1.r 57-1.3.2.2 58-1.3.2.2.2.r 60-1.3.2.2.2 61-1.3.2.2.2.1.r 62-1.3.2.2.2.1.1.1 64-1.3.2.2.2.1.1.1 65-1.3.2.2.2.2.r 66-1.3.2.2.2.2.1.1 67-1.3.2.2.2.2.1 68-1.3.2.2.2.2
(m / multi-sentence
:snt1 (i / increase-01~e.4
:ARG0 (p / protein
:name (n / name :op1 "TNF-α"~e.0))
:ARG1 (p2 / produce-01~e.6
:ARG1~e.7 (p3 / protein
:name (n2 / name :op1 "IL-6"~e.8,10)))
:ARG2 (s / significant-02~e.3)
:location~e.11 (c / cell~e.17
:name (n3 / name :op1 "WI-38-40"~e.12,14,16)))
:snt2 (h / have-concession-91~e.19
:ARG1 (p4 / possible-01~e.24 :polarity~e.23 -~e.23
:ARG1 (i2 / inhibit-01~e.26
:ARG0 (s3 / small-molecule
:name (n4 / name :op1 "DMSO"~e.21))
:ARG1 (e / enhance-01~e.36
:ARG1 (p5 / protein
:name (n5 / name :op1 "IL-6"~e.33,35))
:ARG2-of (i3 / induce-01~e.32
:ARG0 (p6 / protein
:name (n6 / name :op1 "TNF-α"~e.28)))
:location (a / and~e.40
:op1 (l / level~e.42
:mod (p7 / protein~e.39))
:op2 (l2 / level~e.42
:mod (n10 / nucleic-acid
:name (n7 / name :op1 "mRNA"~e.41)))))))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.44 :mod 7~e.46)))
:snt3 (s2 / suggest-01~e.51
:ARG0 (t / thing~e.50
:ARG2-of~e.50 (r2 / result-01~e.50)
:mod (t2 / this~e.49))
:ARG1 (p8 / possible-01~e.54 :polarity~e.55 -~e.55
:ARG1 (i4 / involve-01~e.57
:ARG1 (s4 / small-molecule
:name (n8 / name :op1 "ROI"))
:ARG2~e.58 (p9 / produce-01~e.60
:ARG1~e.61 (p10 / protein
:name (n9 / name :op1 "IL-6"~e.62,64))
:location~e.65 (f2 / fibroblast~e.68
:part-of (l3 / lung~e.67
:part-of (h2 / human~e.66))))))))
# ::id bel_pmid_1036_2713.24538 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok TNF @-@ a was dose dependently capable of inducing IL @-@ 6 release from NHBE and HS @-@ 24 cells ( Fig . 5 , A and C ) .
# ::alignments 0-1.1.1.1.1 4-1.2.2 5-1.2 8-1.1 9-1.1.2.1.1.1 11-1.1.2.1.1.1 12-1.1.2 13-1.1.2.2.r 14-1.1.2.2.1.1.1 15-1.1.2.2 16-1.1.2.2.2.1.1 18-1.1.2.2.2.1.1 19-1.1.2.2.1 19-1.1.2.2.2 21-1.3.1.1 21-1.3.1.2 26-1.3.1
(p / possible-01
:ARG1 (i / induce-01~e.8
:ARG0 (p2 / protein
:name (n / name :op1 "TNF-α"~e.0))
:ARG2 (r / release-01~e.12
:ARG1 (p3 / protein
:name (n2 / name :op1 "IL-6"~e.9,11))
:ARG2~e.13 (a / and~e.15
:op1 (c / cell~e.19
:name (n3 / name :op1 "NHBE"~e.14))
:op2 (c2 / cell~e.19
:name (n4 / name :op1 "HS-24"~e.16,18)))))
:manner (d / depend-01~e.5
:ARG0 p2
:ARG1 (d2 / dose~e.4))
:ARG1-of (d3 / describe-01
:ARG0 (a2 / and~e.26
:op1 (f / figure~e.21 :mod "5A")
:op2 (f2 / figure~e.21 :mod "5C"))))
# ::id bel_pmid_1036_2713.24690 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok As shown in Fig. 3A , stimulation with XO resulted in a significant increase in the levels of IL @-@ 6 at 12 and 24 h compared with those with 0.7 mM X alone ( P , 0.0001 ) . Consistent with these protein data , stimulation of HS @-@ 24 cells with XO caused the maximum elevation in IL @-@ 6 mRNAlevels at 6 h , whereas XO did not modulate control GAPDH transcript levels ( Fig . 3B ) .
# ::alignments 0-1.1.2.3.r 1-1.1.3 2-1.1.3.1.r 3-1.1.3.1 4-1.1.3.1.1 6-1.1.1 8-1.1.1.1.1.1 8-1.1.1.2.1.1.1.1 9-1.1 12-1.1.2.2 13-1.1.2 14-1.1.2.1.r 16-1.1.2.1 17-1.1.2.1.1.r 18-1.1.2.1.1.1.1 20-1.1.2.1.1.1.1 22-1.1.2.3.1.1 23-1.1.2.3 24-1.1.2.3.2.1 25-1.2.1.2.3.2 26-1.1.1.2 28-1.1.1.2.1.2 30-1.1.1.2.1.1.2.1 31-1.1.1.2.1.1.2.2 33-1.1.1.2.1.1.3 35-1.1.1.3 37-1.1.1.3.1.1 40-1.2.3 41-1.2.3.1.r 42-1.2.3.1.2 43-1.2.3.1.1 44-1.2.3.1 46-1.1.1.2.1 46-1.2.1.1 47-1.2.1.1.1.r 48-1.2.1.1.1.1.1 50-1.2.1.1.1.1.1 51-1.2.1.1.1 52-1.2.1.1.2.r 53-1.2.1.1.2.1.1 54-1.2.1 56-1.2.1.2.2 57-1.2.1.2 59-1.2.1.2.1.1.2.1.1.1 61-1.2.1.2.1.1.2.1.1.1 61-1.2.1.2.3.1 64-1.2.1.2.1.1.2.1.1.1 64-1.2.1.2.3.1 65-1.1.2.3.1.2 65-1.2.1.2.3.2 67-1.2 68-1.2.2.2 70-1.2.2.1 70-1.2.2.1.r 71-1.2.2 72-1.2.2.3.1 72-1.2.2.3.1.3 72-1.2.2.3.1.3.r 73-1.2.2.3.1.1.1 75-1.2.1.2.1 75-1.2.2.3 77-1.2.4.1 79-1.2.4.1.1
(m / multi-sentence
:snt1 (r / result-01~e.9
:ARG1 (s / stimulate-01~e.6
:ARG2 (e / enzyme
:name (n / name :op1 "XO"~e.8))
:ARG1-of (c / compare-01~e.26
:ARG2 (s2 / stimulate-01~e.46
:ARG2 (e6 / enzyme
:name (n2 / name :op1 "XO"~e.8)
:quant (c2 / concentration-quantity :quant 0.7~e.30
:unit (m3 / millimolar~e.31))
:mod (a / alone~e.33))
:mod (t / that~e.28)))
:ARG1-of (s6 / statistical-test-91~e.35
:ARG2 (l / less-than :op1 0.0001~e.37)))
:ARG2 (i / increase-01~e.13
:ARG1~e.14 (l2 / level~e.16
:quant-of~e.17 (p2 / protein
:name (n3 / name :op1 "IL-6"~e.18,20)))
:ARG2 (s3 / significant-02~e.12)
:time~e.0 (a2 / and~e.23
:op1 (t2 / temporal-quantity :quant 12~e.22
:unit (h / hour~e.65))
:op2 (t3 / temporal-quantity :quant 24~e.24
:unit h)))
:ARG1-of (s4 / show-01~e.1
:ARG0~e.2 (f / figure~e.3 :mod "3A"~e.4)))
:snt2 (c3 / contrast-01~e.67
:ARG1 (c4 / cause-01~e.54
:ARG0 (s5 / stimulate-01~e.46
:ARG1~e.47 (c5 / cell~e.51
:name (n4 / name :op1 "HS-24"~e.48,50))
:ARG2~e.52 (e2 / enzyme
:name (n5 / name :op1 "XO"~e.53)))
:ARG1 (e3 / elevate-01~e.57
:ARG1 (l3 / level~e.75
:mod (n9 / nucleic-acid
:name (n6 / name :op1 "mRNA")
:ARG0-of (e5 / encode-01
:ARG1 (p4 / protein
:name (n7 / name :op1 "IL-6"~e.59,61,64)))))
:degree (m4 / maximum~e.56)
:quant (t4 / temporal-quantity :quant 6~e.61,64
:unit (h2 / hour~e.25,65))))
:ARG2 (m5 / modulate-01~e.71 :polarity~e.70 -~e.70
:ARG0 e2~e.68
:ARG1 (l4 / level~e.75
:quant-of (e4 / enzyme~e.72
:name (n8 / name :op1 "GAPDH"~e.73)
:ARG1-of (t5 / transcribe-01)
:ARG0-of~e.72 (c6 / control-01~e.72))))
:ARG1-of (c7 / consistent-01~e.40
:ARG2~e.41 (d / data~e.44
:mod (p3 / protein~e.43)
:mod (t6 / this~e.42)))
:ARG1-of (d2 / describe-01
:ARG0 (f2 / figure~e.77 :mod "3B"~e.79))))
# ::id bel_pmid_1036_2713.39152 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok TNF @-@ a significantly increased the production of IL @-@ 6 in WI @-@ 38 @-@ 40 cells . However , DMSO was not able to inhibit the TNF @-@ a @-@ induced IL @-@ 6 enhancement in both protein and mRNA levels ( Fig . 7 ) . These results suggest that ROIs may not be involved in the production of IL @-@ 6 in human lung fibroblasts
# ::alignments 0-1.1.1.1.1 3-1.1.3 4-1.1 6-1.1.2 7-1.1.2.1.r 8-1.1.2.1.1.1 10-1.1.2.1.1.1 11-1.1.4.r 12-1.1.4.1.1 14-1.1.4.1.1 16-1.1.4.1.1 17-1.1.4 19-1.2 21-1.2.1.2.1.1.1 23-1.2.1.1 23-1.2.1.1.r 24-1.2.1 26-1.2.1.2 28-1.2.1.2.2.2.1.1.1 32-1.2.1.2.2.2 33-1.2.1.2.2.1.1.1 35-1.2.1.2.2.1.1.1 36-1.2.1.2.2 39-1.2.1.2.2.3.1.1 40-1.2.1.2.2.3 41-1.2.1.2.2.3.2.1.1.1 42-1.2.1.2.2.3.1 42-1.2.1.2.2.3.2 44-1.2.2.1 46-1.2.2.1.1 49-1.3.1.2 50-1.3.1 50-1.3.1.1 50-1.3.1.1.r 51-1.3 54-1.3.2 55-1.3.2.1 55-1.3.2.1.r 57-1.3.2.2 58-1.3.2.2.2.r 60-1.3.2.2.2 61-1.3.2.2.2.1.r 62-1.3.2.2.2.1.1.1 64-1.3.2.2.2.1.1.1 65-1.3.2.2.2.2.r 66-1.3.2.2.2.2.1.1 67-1.3.2.2.2.2.1 68-1.3.2.2.2.2
(m / multi-sentence
:snt1 (i / increase-01~e.4
:ARG0 (p / protein
:name (n / name :op1 "TNF-α"~e.0))
:ARG1 (p2 / produce-01~e.6
:ARG1~e.7 (p3 / protein
:name (n2 / name :op1 "IL-6"~e.8,10)))
:ARG2 (s / significant-02~e.3)
:location~e.11 (c / cell~e.17
:name (n3 / name :op1 "WI-38-40"~e.12,14,16)))
:snt2 (h / have-concession-91~e.19
:ARG1 (p4 / possible-01~e.24 :polarity~e.23 -~e.23
:ARG1 (i2 / inhibit-01~e.26
:ARG0 (s3 / small-molecule
:name (n4 / name :op1 "DMSO"~e.21))
:ARG1 (e / enhance-01~e.36
:ARG1 (p5 / protein
:name (n5 / name :op1 "IL-6"~e.33,35))
:ARG2-of (i3 / induce-01~e.32
:ARG0 (p6 / protein
:name (n6 / name :op1 "TNF-α"~e.28)))
:location (a / and~e.40
:op1 (l / level~e.42
:quant-of (p7 / protein~e.39))
:op2 (l2 / level~e.42
:quant-of (n10 / nucleic-acid
:name (n7 / name :op1 "mRNA"~e.41)))))))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.44 :mod 7~e.46)))
:snt3 (s2 / suggest-01~e.51
:ARG0 (t / thing~e.50
:ARG2-of~e.50 (r2 / result-01~e.50)
:mod (t2 / this~e.49))
:ARG1 (p8 / possible-01~e.54 :polarity~e.55 -~e.55
:ARG1 (i4 / involve-01~e.57
:ARG1 (s4 / small-molecule
:name (n8 / name :op1 "ROI"))
:ARG2~e.58 (p9 / produce-01~e.60
:ARG1~e.61 (p10 / protein
:name (n9 / name :op1 "IL-6"~e.62,64))
:location~e.65 (f2 / fibroblast~e.68
:part-of (l3 / lung~e.67
:part-of (h2 / human~e.66))))))))
# ::id bel_pmid_1036_2713.39154 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok TNF @-@ a was dose dependently capable of inducing IL @-@ 6 release from NHBE and HS @-@ 24 cells ( Fig . 5 , A and C ) .
# ::alignments 0-1.1.1.1.1 4-1.2.2 5-1.2 8-1.1 9-1.1.2.1.1.1 11-1.1.2.1.1.1 12-1.1.2 13-1.1.2.2.r 14-1.1.2.2.1.1.1 15-1.1.2.2 16-1.1.2.2.2.1.1 18-1.1.2.2.2.1.1 19-1.1.2.2.1 19-1.1.2.2.2 21-1.3.1.1 21-1.3.1.2 26-1.3.1
(p / possible-01
:ARG1 (i / induce-01~e.8
:ARG0 (p2 / protein
:name (n / name :op1 "TNF-α"~e.0))
:ARG2 (r / release-01~e.12
:ARG1 (p3 / protein
:name (n2 / name :op1 "IL-6"~e.9,11))
:ARG2~e.13 (a / and~e.15
:op1 (c / cell~e.19
:name (n3 / name :op1 "NHBE"~e.14))
:op2 (c2 / cell~e.19
:name (n4 / name :op1 "HS-24"~e.16,18)))))
:manner (d / depend-01~e.5
:ARG0 p2
:ARG1 (d2 / dose~e.4))
:ARG1-of (d3 / describe-01
:ARG0 (a2 / and~e.26
:op1 (f / figure~e.21 :mod "5A")
:op2 (f2 / figure~e.21 :mod "5C"))))
# ::id bel_pmid_1037_5612.23694 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Northern blot analysis documented that two transcription factor genes chosen for further study , c @-@ myc promoter @-@ binding protein ( MBP @-@ 1 ) and X @-@ box binding protein 1 ( XBP @-@ 1 ) , were up @-@ regulated in U266 cells about 3 @-@ fold relative to the cell cycle @-@ dependent beta @-@ actin gene 12 h after IL @-@ 6 treatment .
# ::alignments 0-1.1.1.1.1 1-1.1.1.1.2 2-1.1 3-1 5-1.2.1.1 6-1.2.1.2.1 7-1.2.1.2.2 8-1.2.1 9-1.2.1.3 10-1.2.1.3.1.r 11-1.2.1.3.1.1 12-1.2.1.3.1 14-1.2.1.4.1.1.1.1.1.1.1.1 16-1.2.1.4.1.1.1.1.1.1.1.1 17-1.2.1.4.1.1.1.1 17-1.2.1.4.1.1.1.1.1 17-1.2.1.4.1.1.1.1.1.r 19-1.2.1.4.1.1.1 20-1.2.1.4.1.1 22-1.2.1.4.1.1.2.1.1.1 24-1.2.1.4.1.1.2.1.1.1 24-1.2.1.4.1.2.1.4 26-1.2.1.4.1 27-1.2.1.4.1.2.1.1 29-1.2.1.4.1.2.1.1 30-1.2.1.4.1.2.1.2 31-1.2.1.4.1.2.1.3 32-1.2.1.4.1.2.1.4 32-1.2.1.4.1.2.2.1.1.1 34-1.2.1.4.1.2.2.1.1.1 36-1.2.1.4.1.1.2.1.1.1 36-1.2.1.4.1.2.2.1.1.1 44-1.2.2.1.1 45-1.2.2 46-1.2.3.2 47-1.2.3.1 49-1.2.3 50-1.2.5 51-1.2.5.1.r 53-1.2.5.1.2.1.1 54-1.2.5.1.2.1 56-1.2.5.1.2 57-1.2.5.1.1.1 59-1.2.5.1.1.1 60-1.2.5.1 61-1.2.4.2.1 62-1.2.4.2.2 63-1.2.4 64-1.2.4.1.1.1.1 66-1.2.4.1.1.1.1 67-1.2.4.1
(d / document-01~e.3
:ARG0 (a / analyze-01~e.2
:instrument (t / thing
:name (n / name :op1 "northern"~e.0 :op2 "blot"~e.1)))
:ARG1 (u / upregulate-01
:ARG1 (g / gene~e.8 :quant 2~e.5
:name (n2 / name :op1 "transcription"~e.6 :op2 "factor"~e.7)
:ARG1-of (c / choose-01~e.9
:ARG4~e.10 (s / study-01~e.12
:degree (f / further~e.11)))
:ARG1-of (m / mean-01
:ARG2 (a2 / and~e.26
:op1 (p / protein~e.20
:ARG0-of (b / bind-01~e.19
:ARG1 (m3 / molecular-physical-entity~e.17
:ARG0-of~e.17 (p8 / promote-01~e.17
:ARG1 (p2 / protein
:name (n3 / name :op1 "c-myc"~e.14,16)))))
:ARG1-of (d2 / describe-01
:ARG0 (p3 / protein
:name (n4 / name :op1 "MBP-1"~e.22,24,36))))
:op2 (p9 / protein
:name (n11 / name :op1 "X-box"~e.27,29 :op2 "binding"~e.30 :op3 "protein"~e.31 :op4 1~e.24,32)
:ARG1-of (d3 / describe-01
:ARG0 (p5 / protein
:name (n7 / name :op1 "XBP-1"~e.32,34,36)))))))
:location (c2 / cell~e.45
:name (n8 / name :op1 "U266"~e.44))
:degree (p6 / product-of~e.49 :op1 3~e.47
:mod (a3 / about~e.46))
:time (a4 / after~e.63
:op1 (t2 / treat-04~e.67
:ARG2 (p7 / protein
:name (n9 / name :op1 "IL-6"~e.64,66)))
:quant (t3 / temporal-quantity :quant 12~e.61
:unit (h / hour~e.62)))
:ARG2-of (r / relative-05~e.50
:ARG3~e.51 (g2 / gene~e.60
:name (n10 / name :op1 "beta-actin"~e.57,59)
:ARG0-of (d4 / depend-01~e.56
:ARG1 (c3 / cycle-02~e.54
:ARG1 (c4 / cell~e.53)))))))
# ::id bel_pmid_1040_9724.52 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Signaling by the IL @-@ 6 receptor is mediated through the signal transducing subunit gp130 and involves the activation of Janus @-@ associated kinases ( JAKs ) , signal transducer and activator of transcription 3 ( STAT3 ) , and mitogen @-@ activated protein ( MAP ) kinase .
# ::alignments 0-1.1.1 3-1.1.1.1.1.1 5-1.1.1.1.1.1 6-1.1.1.1 8-1.1 11-1.1.1 11-1.1.2.2.1.1 12-1.1.2.2.1 13-1.1.2.2 14-1.1.2.1.1 15-1 16-1.2 18-1.2.1 19-1.2.1.1.2.1.5 19-1.2.1.1.r 20-1.2.1.1.1.1.1 22-1.2.1.1.1.1.1 23-1.2.1.1.1.1.2 25-1.2.1.1.1.2.1.1.1 28-1.2.1.1.2.1.1 29-1.2.1.1.2.1.2 30-1.2.1.1.2.1.3 31-1.2.1.1.2.1.4 32-1.2.1.1.2.1.5 33-1.2.1.1.2.1.6 34-1.2.1.1.2.1.6 36-1.2.1.1.2.2.1.1.1 39-1.2.1.1 40-1.2.1.1.3.1.1 42-1.2.1.1.3.1.1 43-1.2.1.1.3.1.2 45-1.2.1.1.3.2.1.1.1 47-1.2.1.1.3.1.3
(a / and~e.15
:op1 (m / mediate-01~e.8
:ARG1 (s / signal-07~e.0,11
:ARG0 (r / receptor~e.6
:name (n / name :op1 "IL-6"~e.3,5)))
:medium (p / protein
:name (n2 / name :op1 "gp130"~e.14)
:mod (s2 / subunit~e.13
:ARG2-of (t / transduce-01~e.12
:ARG1 (s3 / signal-07~e.11)))))
:op2 (i / involve-01~e.16
:ARG1 (a2 / activate-01~e.18
:ARG1~e.19 (a3 / and~e.39
:op1 (e / enzyme
:name (n3 / name :op1 "Janus-associated"~e.20,22 :op2 "kinase"~e.23)
:ARG1-of (d / describe-01
:ARG0 (e2 / enzyme
:name (n4 / name :op1 "JAK"~e.25))))
:op2 (p2 / protein
:name (n5 / name :op1 "signal"~e.28 :op2 "transducer"~e.29 :op3 "and"~e.30 :op4 "activator"~e.31 :op5 "of"~e.19,32 :op6 "transcription-3"~e.33,34)
:ARG1-of (d2 / describe-01
:ARG0 (p3 / protein
:name (n6 / name :op1 "STAT3"~e.36))))
:op3 (e3 / enzyme
:name (n7 / name :op1 "mitogen-activated"~e.40,42 :op2 "protein"~e.43 :op3 "kinase"~e.47)
:ARG1-of (d3 / describe-01
:ARG0 (e4 / enzyme
:name (n8 / name :op1 "MAP"~e.45))))))
:ARG2 s))
# ::id bel_pmid_1040_9724.18580 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Signaling by the IL @-@ 6 receptor is mediated through the signal transducing subunit gp130 and involves the activation of Janus @-@ associated kinases ( JAKs ) , signal transducer and activator of transcription 3 ( STAT3 ) , and mitogen @-@ activated protein ( MAP ) kinase .
# ::alignments 0-1.1.1 3-1.1.1.1.1.1 5-1.1.1.1.1.1 6-1.1.1.1 8-1.1 11-1.1.1 11-1.1.2.2.1.1 12-1.1.2.2.1 13-1.1.2.2 14-1.1.2.1.1 15-1 16-1.2 18-1.2.1 19-1.2.1.1.2.1.5 19-1.2.1.1.r 20-1.2.1.1.1.1.1 22-1.2.1.1.1.1.1 23-1.2.1.1.1.1.2 25-1.2.1.1.1.2.1.1.1 28-1.2.1.1.2.1.1 29-1.2.1.1.2.1.2 30-1.2.1.1.2.1.3 31-1.2.1.1.2.1.4 32-1.2.1.1.2.1.5 33-1.2.1.1.2.1.6 34-1.2.1.1.2.1.6 36-1.2.1.1.2.2.1.1.1 39-1.2.1.1 40-1.2.1.1.3.1.1 42-1.2.1.1.3.1.1 43-1.2.1.1.3.1.2 45-1.2.1.1.3.2.1.1.1 47-1.2.1.1.3.1.3
(a / and~e.15
:op1 (m / mediate-01~e.8
:ARG1 (s / signal-07~e.0,11
:ARG0 (r / receptor~e.6
:name (n / name :op1 "IL-6"~e.3,5)))
:medium (p / protein
:name (n2 / name :op1 "gp130"~e.14)
:mod (s2 / subunit~e.13
:ARG2-of (t / transduce-01~e.12
:ARG1 (s3 / signal-07~e.11)))))
:op2 (i / involve-01~e.16
:ARG1 (a2 / activate-01~e.18
:ARG1~e.19 (a3 / and~e.39
:op1 (e / enzyme
:name (n3 / name :op1 "Janus-associated"~e.20,22 :op2 "kinase"~e.23)
:ARG1-of (d / describe-01
:ARG0 (e2 / enzyme
:name (n4 / name :op1 "JAK"~e.25))))
:op2 (p2 / protein
:name (n5 / name :op1 "signal"~e.28 :op2 "transducer"~e.29 :op3 "and"~e.30 :op4 "activator"~e.31 :op5 "of"~e.19,32 :op6 "transcription-3"~e.33,34)
:ARG1-of (d2 / describe-01
:ARG0 (p3 / protein
:name (n6 / name :op1 "STAT3"~e.36))))
:op3 (e3 / enzyme
:name (n7 / name :op1 "mitogen-activated"~e.40,42 :op2 "protein"~e.43 :op3 "kinase"~e.47)
:ARG1-of (d3 / describe-01
:ARG0 (e4 / enzyme
:name (n8 / name :op1 "MAP"~e.45))))))
:ARG2 s))
# ::id bel_pmid_1040_9724.23704 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok This study shows that in hepatoma cells , the recruitment and tyrosine phosphorylation of SHP @-@ 2 , but not SHC , is the primary signaling event associated with the activation of MAP kinases ( ERK1 @/@ 2 ) by gp130 .
# ::alignments 0-1.1.1 1-1.1 2-1 4-1.2.r 5-1.2.4.2.1.1.1 6-1.2.4.2 9-1.2.3.1 9-1.2.3.3.1.1 10-1.2.3 11-1.2.3.2.2 12-1.2.3.2 12-1.2.3.3.1.2 13-1.2.3.1.1.r 14-1.2.3.1.1.1.1 16-1.2.3.1.1.1.1 18-1.2.3.3 19-1.2.3.3.1.1.1 19-1.2.3.3.1.1.1.r 19-1.2.3.3.1.2.1 19-1.2.3.3.1.2.1.r 20-1.2.3.3.1.1.2.1.1 22-1.2.3.r 24-1.2.2 25-1.2.1 26-1.2 27-1.2.4 28-1.2.4.1.r 30-1.2.4.1 31-1.2.4.1.2.r 32-1.2.4.1.2.1.1 33-1.2.4.1.2.1.2 37-1.2.3.1.1.1.1 39-1.2.4.1.1.r 40-1.2.4.1.1.1.1
(s / show-01~e.2
:ARG0 (s2 / study-01~e.1
:mod (t / this~e.0))
:ARG1~e.4 (e / event~e.26
:ARG0-of (s3 / signal-07~e.25)
:mod (p / primary~e.24)
:domain~e.22 (a / and~e.10
:op1 (r / recruit-01~e.9
:ARG1~e.13 (p2 / protein
:name (n / name :op1 "SHP-2"~e.14,16,37)))
:op2 (p3 / phosphorylate-01~e.12
:ARG1 p2
:ARG2 (t2 / tyrosine~e.11))
:ARG1-of (c / contrast-01~e.18
:ARG2 (a2 / and
:op1 (r2 / recruit-01~e.9 :polarity~e.19 -~e.19
:ARG1 (p4 / protein
:name (n2 / name :op1 "SHC"~e.20)))
:op2 (p5 / phosphorylate-01~e.12 :polarity~e.19 -~e.19
:ARG1 p4
:ARG2 t2))))
:ARG1-of (a3 / associate-01~e.27
:ARG2~e.28 (a4 / activate-01~e.30
:ARG0~e.39 (p6 / protein
:name (n3 / name :op1 "gp130"~e.40))
:ARG1~e.31 (p7 / protein-family
:name (n4 / name :op1 "MAP"~e.32 :op2 "kinase"~e.33)))
:location (c2 / cell~e.6
:mod (m / medical-condition
:name (n6 / name :op1 "hepatoma"~e.5))))))
# ::id bel_pmid_1043_6166.3510 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok NO modulation of the signaling pathway was shown by its inhibitory effect on shear stress @-@ induced ERK1 @/@ ERK2 phosphorylation and activity .
# ::alignments 0-1.2.1.1 1-1.2 2-1.2.2.r 4-1.2.2.1 5-1.2.2 7-1 10-1.1.3 11-1.1 12-1.1.2.r 13-1.1.2.1.1.3.1.1 14-1.1.2.1.1.3.1 16-1.1.2.1.1.3 17-1.1.2.1.1.1.1.1 18-1.1.2.1.1 19-1.1.2.1.1.2.1.1 20-1.1.2.1 21-1.1.2 22-1.1.2.2
(s / show-01~e.7
:ARG0 (a3 / affect-01~e.11
:ARG0 m2
:ARG1~e.12 (a / and~e.21
:op1 (p / phosphorylate-01~e.20
:ARG1 (s3 / slash~e.18
:op1 (e2 / enzyme
:name (n2 / name :op1 "ERK1"~e.17))
:op2 (e3 / enzyme
:name (n3 / name :op1 "ERK2"~e.19))
:ARG2-of (i2 / induce-01~e.16
:ARG0 (s4 / stress-02~e.14
:mod (s5 / shear-01~e.13)))))
:op2 (a2 / activity-06~e.22
:ARG0 s3))
:ARG2 (i / inhibit-01~e.10
:ARG1 p))
:ARG1 (m2 / modulate-01~e.1
:ARG0 (n / name :op1 "NO"~e.0)
:ARG1~e.2 (p2 / pathway~e.5
:ARG0-of (s2 / signal-07~e.4))))
# ::id bel_pmid_1043_6166.18636 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Treatment of ECs with an NO donor , S @-@ nitroso @-@ N @-@ acetylpenicillamine ( SNAP ) or 3 @-@ morpholinosydnonimine ( SIN @-@ 1 ) , inhibited this shear stress @-@ induced Egr @-@ 1 expression .
# ::alignments 0-1.1 6-1.1.2 6-1.1.2.2 6-1.1.2.2.r 8-1.1.2.3.1.1.1 10-1.1.2.3.1.1.1 12-1.1.2.3.1.1.1 14-1.1.2.3.1.1.1 16-1.1.2.3.1.2.1.1 18-1.1.2.3 19-1.1.2.3.2.1.1 21-1.1.2.3.2.1.1 23-1.1.2.3.2.2.1.1 25-1.1.2.3.2.2.1.1 28-1 29-1.2.2 30-1.2.1.2.1.1 31-1.2.1.2.1 33-1.2.1.2 34-1.2.1.1.1 36-1.2.1.1.1 37-1.2
(i3 / inhibit-01~e.28
:ARG0 (t / treat-04~e.0
:ARG1 (c / cell
:name (n / name :op1 "EC"))
:ARG2 (s3 / small-molecule~e.6
:name (n8 / name :op1 "nitric" :op2 "oxide")
:ARG0-of~e.6 (d / donate-01~e.6)
:example (o / or~e.18
:op1 (s4 / small-molecule
:name (n3 / name :op1 "S-nitroso-N-acetylpenicillamine"~e.8,10,12,14)
:ARG1-of (m / mean-01
:ARG2 (n4 / name :op1 "SNAP"~e.16)))
:op2 (s5 / small-molecule
:name (n5 / name :op1 "3-morpholinosydnonimine"~e.19,21)
:ARG1-of (m2 / mean-01
:ARG2 (n6 / name :op1 "SIN-1"~e.23,25))))))
:ARG1 (e / express-03~e.37
:ARG2 (p2 / protein
:name (n7 / name :op1 "Egr-1"~e.34,36)
:ARG2-of (i2 / induce-01~e.33
:ARG0 (s / stress-02~e.31
:mod (s2 / shear-01~e.30))))
:mod (t2 / this~e.29)))
# ::id bel_pmid_1044_6041.18010 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The FAK and Fyn @/@ Shc pathways . Integrins activate various protein tyrosine kinases , including focal adhesion kinase ( FAK ) , Srcfamily kinases , and Abl , and a serine @-@ threonine kinase , integrin @-@ linked kinase ( ILK ) ( 4 , 7 ) .
# ::alignments 1-1.1.1.1.1 2-1.1 3-1.1.2.1.1 5-1.1.2.1.1 6-1.1.1 6-1.1.2 8-1.2.1.1.1 9-1.2 10-1.2.2.1.3 11-1.2.2.1.1.1 12-1.2.2.1.1.2 13-1.2.2.1.1.3 15-1.2.2.1.2 16-1.2.2.1.2.1.1.1.1 17-1.2.2.1.2.1.1.1.2 18-1.2.2.1.2.1.1.1.3 20-1.2.2.1.2.1.1.2.1.1 26-1.2.2.1.2.1 27-1.2.2.1.2.1.3.1.1 29-1.2.2.1.2.1 31-1.2.2.2.1.1 33-1.2.2.2.1.1 34-1.2.2.2.1.2 34-1.2.2.2.2.1.1.2 36-1.2.2.2.2.1.1.1 38-1.2.2.2.2.1.1.1 39-1.2.2.2.2.1.1.2 44-1.2.3.1.1.1.1 46-1.2.3.1.1.1.2
(m / multi-sentence
:snt1 (a / and~e.2
:op1 (p / pathway~e.6
:name (n / name :op1 "FAK"~e.1))
:op2 (p2 / pathway~e.6
:name (n2 / name :op1 "Fyn/Shc"~e.3,5)))
:snt2 (a2 / activate-01~e.9
:ARG0 (p7 / protein
:name (n3 / name :op1 "integrin"~e.8))
:ARG1 (a3 / and
:op1 (e3 / enzyme
:name (n10 / name :op1 "protein"~e.11 :op2 "tyrosine"~e.12 :op3 "kinase"~e.13)
:ARG2-of (i2 / include-91~e.15
:ARG1 (a4 / and~e.26,29
:op1 (e2 / enzyme
:name (n4 / name :op1 "focal"~e.16 :op2 "adhesion"~e.17 :op3 "kinase"~e.18)
:ARG1-of (m2 / mean-01
:ARG2 (n5 / name :op1 "FAK"~e.20)))
:op2 (p3 / protein-family
:name (n9 / name :op1 "Src"))
:op3 (p4 / protein
:name (n6 / name :op1 "Abl"~e.27))))
:mod (v2 / various~e.10))
:op2 (e / enzyme
:name (n7 / name :op1 "serine-threonine"~e.31,33 :op2 "kinase"~e.34)
:ARG1-of (m5 / mean-01
:ARG2 (e4 / enzyme
:name (n8 / name :op1 "integrin-linked"~e.36,38 :op2 "kinase"~e.34,39)))))
:ARG1-of (d / describe-01
:ARG0 (p6 / publication
:ARG1-of (c / cite-01
:ARG2 (a5 / and :op1 4~e.44 :op2 7~e.46))))))
# ::id bel_pmid_1044_6041.18016 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok ( 38 ) . Integrins also stimulate the p70 S6 @- kinase , which may promote cyclin D1 translation ( 39 ) . Finally , anchorage to the ECM is necessary for the down @-@ regulation of the Cdk 2 inhibitors p21 and p27 and , thus , the activation of cyclin E @-@ Cdk 2
# ::alignments 1-1.1.1.1.1 4-1.2.1.1.1 5-1.2.3 6-1.2 8-1.2.2.1.1 9-1.2.2.1.2 11-1.2.2.1.3 14-1.2.4.2 15-1.2.4 16-1.2.4.1.1.1.1 17-1.2.4.1.1.1.2 18-1.2.4.1 20-1.2.5.1.1.1 23-1.3.1 23-1.3.1.r 26-1.3.4 30-1.3 31-1.3.2.r 33-1.3.2 34-1.3.2 35-1.3.2 38-1.3.4.1.1.1.2 39-1.3.4.1.1.1.3 40-1.3.2.1.1 40-1.3.2.1.1.2 40-1.3.2.1.1.2.r 40-1.3.2.1.2 40-1.3.2.1.2.2 40-1.3.2.1.2.2.r 41-1.3.2.1.1.1.1 42-1.3.2.1 43-1.3.2.1.2.1.1 44-1.3.2.1 46-1.3.4 49-1.3.4.1 51-1.3.4.1.1.1.1 52-1.3.4.1.1.1.2 54-1.3.2.1.1.2.1.1.1 55-1.3.2.1.1.2.1.1.2
(m / multi-sentence
:snt1 (d2 / describe-01
:ARG0 (p / publication
:ARG1-of (c / cite-01 :ARG2 38~e.1)))
:snt2 (s / stimulate-01~e.6
:ARG0 (p8 / protein
:name (n10 / name :op1 "integrin"~e.4))
:ARG2 (e / enzyme
:name (n2 / name :op1 "p70"~e.8 :op2 "S6"~e.9 :op3 "kinase"~e.11))
:mod (a / also~e.5)
:ARG0-of (p2 / promote-01~e.15
:ARG1 (t2 / translate-01~e.18
:ARG2 (p4 / protein
:name (n3 / name :op1 "cyclin"~e.16 :op2 "D1"~e.17)))
:ARG1-of (p3 / possible-01~e.14))
:ARG1-of (d3 / describe-01
:ARG0 (p5 / publication
:ARG1-of (c2 / cite-01 :ARG2 39~e.20))))
:snt3 (n / need-01~e.30 :li~e.23 -1~e.23
:ARG0~e.31 (d4 / downregulate-01~e.33,34,35
:ARG1 (a3 / and~e.42,44
:op1 (p6 / protein~e.40
:name (n6 / name :op1 "p21"~e.41)
:ARG0-of~e.40 (i / inhibit-01~e.40
:ARG1 (e2 / enzyme
:name (n7 / name :op1 "Cdk"~e.54 :op2 2~e.55))))
:op2 (p7 / protein~e.40
:name (n8 / name :op1 "p27"~e.43)
:ARG0-of~e.40 (i3 / inhibit-01~e.40
:ARG1 e2))))
:ARG1 (a2 / anchor-01
:ARG1 (m2 / matrix
:mod (e4 / extracellular)))
:ARG0-of (c3 / cause-01~e.26,46
:ARG1 (a4 / activate-01~e.49
:ARG1 (e3 / enzyme
:name (n9 / name :op1 "cyclin"~e.51 :op2 "E-Cdk"~e.38,52 :op3 2~e.39))))))
# ::id bel_pmid_1044_6041.18018 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok PTP @-@ PEST has a COOH @-@ terminal extension that anchors it to the cytosolic aspect of the endoplasmic reticulum . Integrin @-@ mediated adhesion activates calpain , a protease that cleaves this extension and allows the phosphatase to relocate to focal adhesions ( 21 ) .
# ::alignments 0-1.1.1.1.1 2-1.1.1.1.1 3-1.1 5-1.1.2.1.1.1 7-1.1.2.1.1.1 8-1.1.2 10-1.1.2.2 11-1.1.2.2.1 12-1.1.2.2.2.r 14-1.1.2.2.2.1 15-1.1.2.2.2 16-1.1.2.2.2.2.r 18-1.1.2.2.2.2.1 19-1.1.2.2.2.2 21-1.2.1.1.1.1.1 23-1.2.1.1 24-1.2.1 25-1.2 26-1.2.2.1.1 29-1.2.2 31-1.2.2.2 32-1.2.2.2.1.1 33-1.2.2.2.1 35-1.2.2.3 37-1.2.2.3.1.1.1.1 39-1.2.2.3.1 40-1.2.2.3.1.2.r 41-1.2.2.3.1.2.1 42-1.2.2.3.1.2 44-1.2.3.1.1.1
(m / multi-sentence
:snt1 (h / have-03~e.3
:ARG0 (e4 / enzyme
:name (n / name :op1 "PTP-PEST"~e.0,2))
:ARG1 (e / extend-01~e.8
:mod (p2 / protein-segment
:name (n2 / name :op1 "COOH-terminus"~e.5,7))
:ARG0-of (a / anchor-01~e.10
:ARG1 e4~e.11
:location~e.12 (a2 / aspect~e.15
:mod (c / cytosol~e.14)
:part-of~e.16 (r / reticulum~e.19
:mod (e2 / endoplasm~e.18))))))
:snt2 (a3 / activate-01~e.25
:ARG0 (a4 / adhere-01~e.24
:ARG1-of (m2 / mediate-01~e.23
:ARG0 (p3 / protein
:name (n5 / name :op1 "integrin"~e.21))))
:ARG1 (p / protease~e.29
:name (n6 / name :op1 "calpain"~e.26)
:ARG0-of (c2 / cleave-01~e.31
:ARG1 (e5 / extend-01~e.33
:mod (t / this~e.32)))
:ARG0-of (a5 / allow-01~e.35
:ARG1 (r2 / relocate-01~e.39
:ARG1 (e3 / enzyme
:name (n4 / name :op1 "phosphatase"~e.37))
:ARG2~e.40 (a6 / adhere-01~e.42
:mod (f / focal~e.41)))))
:ARG1-of (d / describe-01
:ARG0 (p5 / publication
:ARG1-of (c3 / cite-01 :ARG2 21~e.44)))))
# ::id bel_pmid_1044_6041.18060 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Whereas FAK is phosphorylated on tyrosine upon assembly of focal adhesions , it becomes phosphorylated on serine and disassociates from Src and p130CAS during mitosis ( 14 ) . These events may loosen cell @-@ substrate contacts and allow cells to divide and move apart .
# ::alignments 0-1.1 1-1.1.1.1.2.1.1 3-1.1.1 5-1.1.1.1.1.1 7-1.1.1.2 8-1.1.1.2.1.r 9-1.1.1.2.1.1 10-1.1.1.2.1 13-1.1.2.1 14-1.1.2.1.1 15-1.1.2.1.1.1.r 16-1.1.2.1.1.1.1.1 17-1.1.2 18-1.1.2.2 19-1.1.2.2.2.r 20-1.1.2.2.2.1.1.1 22-1.1.2.2.2.2.1.1 23-1.1.2.2.3.r 24-1.1.2.2.3 26-1.1.3.1.1.1 29-1.2.1.1.1.1 30-1.2.1.1.1 31-1.2.1 32-1.2.1.1 33-1.2.1.1.2.1 35-1.2.1.1.2.2 36-1.2.1.1.2 37-1.2 38-1.2.2 39-1.2.2.2.1.1 41-1.2.2.2.1 42-1.2.2.2 43-1.2.2.2.2 44-1.2.2.2.2.2
(m / multi-sentence
:snt1 (c / contrast-01~e.0
:ARG1 (p / phosphorylate-01~e.3
:ARG1 (a2 / amino-acid
:name (n3 / name :op1 "tyrosine"~e.5)
:part-of (e2 / enzyme
:name (n2 / name :op1 "FAK"~e.1)))
:time (a3 / assemble-02~e.7
:ARG1~e.8 (a4 / adhere-01~e.10
:mod (f / focal~e.9))))
:ARG2 (a6 / and~e.17
:op1 (b / become-01~e.13
:ARG1 (p3 / phosphorylate-01~e.14
:ARG1~e.15 (a / amino-acid
:name (n / name :op1 "serine"~e.16)
:part-of e2)))
:op2 (d2 / disassociate-01~e.18
:ARG1 e2
:ARG2~e.19 (a5 / and
:op1 (p4 / protein
:name (n4 / name :op1 "Src"~e.20))
:op2 (p5 / protein
:name (n5 / name :op1 "p130CAS"~e.22)))
:time~e.23 (m2 / mitosis~e.24)))
:ARG1-of (d3 / describe-01
:ARG0 (p6 / publication
:ARG1-of (c2 / cite-01 :ARG2 14~e.26))))
:snt2 (a7 / and~e.37
:op1 (p7 / possible-01~e.31
:ARG1 (l / loosen-01~e.32
:ARG0 (e / event~e.30
:mod (t / this~e.29))
:ARG1 (c3 / contact-01~e.36
:ARG0 (c4 / cell~e.33)
:ARG1 (s / substrate~e.35))))
:op2 (a8 / allow-01~e.38
:ARG0 e
:ARG1 (a9 / and~e.42
:op1 (d4 / divide-02~e.41
:ARG0 (c5 / cell~e.39)
:ARG1 c5)
:op2 (m3 / move-01~e.43
:ARG1 c5
:mod (a10 / apart~e.44))))))
# ::id bel_pmid_1044_6041.18334 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Certain integrins may regulate proliferation by additional mechanisms . For example , the a6b1 integrin may in part promote exit from the cell cycle in myoblasts , because the cytoplasmic domain of a6 inhibits paxillin signaling ( 44 ) .
# ::alignments 0-1.2.1.1.2 1-1.2.1.1.1.1 2-1.2 3-1.2.1 4-1.2.1.2 5-1.2.1.3.r 6-1.2.1.3.1 7-1.2.1.3 9-1.1.3 10-1.1.3 13-1.1.2.1.1.1.1 14-1.1.2.1.1.1.2 15-1.1.2 16-1.1.2.1.3.r 17-1.1.2.1.3 17-1.1.2.1.3.r 18-1.1.2.1 19-1.1.2.1.2 20-1.1.2.1.2.1.r 22-1.1.2.1.2.1.1 23-1.1.2.1.2.1 27-1.1 29-1.1.1.1.1 30-1.1.1.1 33-1.1.1 34-1.1.1.2.1.1.1 35-1.1.1.2 37-1.1.4.1.1.1
(m / multi-sentence
:snt2 (c2 / cause-01~e.27
:ARG0 (i3 / inhibit-01~e.33
:ARG0 (d2 / domain~e.30
:mod (c5 / cytoplasm~e.29)
:part-of p6)
:ARG1 (s / signal-07~e.35
:ARG0 (p5 / protein
:name (n3 / name :op1 "paxillin"~e.34))))
:ARG1 (p / possible-01~e.15
:ARG1 (p3 / promote-01~e.18
:ARG0 (p6 / protein
:name (n2 / name :op1 "a6b1"~e.13 :op2 "integrin"~e.14))
:ARG1 (e2 / exit-01~e.19
:ARG1~e.20 (c3 / cycle-02~e.23
:ARG1 (c4 / cell~e.22)
:location (m3 / myoblast)))
:degree~e.16,17 (p4 / part~e.17)))
:ARG0-of (e / exemplify-01~e.9,10)
:ARG1-of (d3 / describe-01
:ARG0 (p7 / publication
:ARG1-of (c6 / cite-01 :ARG2 44~e.37))))
:snt1 (p8 / possible-01~e.2
:ARG1 (r / regulate-01~e.3
:ARG0 (p9 / protein
:name (n / name :op1 "integrin"~e.1)
:mod (c / certain~e.0))
:ARG1 (p2 / proliferate-01~e.4)
:instrument~e.5 (m2 / mechanism~e.7
:mod (a / additional~e.6)))))
# ::id bel_pmid_1044_6041.18348 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok For example , avb3 associates with the PDGF receptor , and fibroblasts show greater proliferation in response to PDGFb when adhering to the avb3 ligand vitronectin than when they adhere to the b1 integrin ligand collagen ( 26 ) .
# ::alignments 0-1.3 1-1.3 3-1.1.1.1.1 4-1.1 5-1.1.2.r 7-1.1.2.1.1 8-1.1.2.1.2 10-1 11-1.2.1.1.1 12-1.2 13-1.2.2.1 13-1.2.2.1.1 13-1.2.2.1.1.r 14-1.2.2 15-1.2.3.r 16-1.2.3 17-1.2.3.1.r 18-1.2.3.1.1.1 19-1.2.4.r 20-1.2.4 20-1.2.4.3 23-1.1.1.1.1 25-1.2.4.2.1.1 26-1.2.4.3.r 27-1.2.4.r 29-1.2.4 29-1.2.4.3 30-1.2.4.3.2.r 32-1.2.4.3.2.2.1.1.1 33-1.2.4.3.2.2.1.1.2 35-1.2.4.3.2.1.1 37-1.4.1.1.1
(a / and~e.10
:op1 (a2 / associate-01~e.4
:ARG1 (p4 / protein
:name (n9 / name :op1 "avb3"~e.3,23))
:ARG2~e.5 (p8 / protein
:name (n5 / name :op1 "PDGF"~e.7 :op2 "receptor"~e.8)))
:op2 (s / show-01~e.12
:ARG0 (c / cell
:name (n2 / name :op1 "fibroblast"~e.11))
:ARG1 (p / proliferate-01~e.14
:mod (g2 / great~e.13
:degree~e.13 (m / more~e.13)))
:ARG2-of~e.15 (r2 / respond-01~e.16
:ARG1~e.17 (p2 / protein
:name (n3 / name :op1 "PDGFb"~e.18)))
:time~e.19,27 (a4 / adhere-01~e.20,29
:ARG1 p2
:ARG2 (p7 / protein
:name (n6 / name :op1 "vitronectin"~e.25)
:ARG1-of (b2 / bind-01
:ARG2 p4))
:compared-to~e.26 (a5 / adhere-01~e.20,29
:ARG1 p2
:ARG2~e.30 (p5 / protein
:name (n4 / name :op1 "collagen"~e.35)
:ARG1-of (b / bind-01
:ARG2 (p3 / protein
:name (n8 / name :op1 "b1"~e.32 :op2 "integrin"~e.33)))))))
:ARG0-of (e / exemplify-01~e.0,1)
:ARG1-of (d / describe-01
:ARG0 (p6 / publication
:ARG1-of (c2 / cite-01 :ARG2 26~e.37))))
# ::id bel_pmid_1044_6041.18586 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In addition to activating FAK , some b1 and av integrins also activate the tyrosine kinase Fyn and , through it , the adapter protein Shc ( 4 ) .
# ::alignments 0-1.2 1-1 1-1.2 1-1.2.r 3-1.1 3-1.2.1 3-1.2.3 4-1.1.1.1.1 6-1.2.1.1.2 7-1.2.1.1.1.1 7-1.2.2.1.1.1 10-1.2.1.1.1.2 10-1.2.2.1.1.2 11-1.2.1.3 12-1.2.1 12-1.2.2 14-1.2.1.2.1.1 15-1.2.1.2.1.2 16-1.2.1.2.1.3 17-1.2 23-1.2.3.1.2 24-1.2.1.1 24-1.2.2.1 24-1.2.3.1 25-1.2.3.1.1.1 27-1.3.1.1.1
(a / and~e.1
:op1 (a2 / activate-01~e.3
:ARG1 (e2 / enzyme
:name (n / name :op1 "FAK"~e.4)))
:op2~e.1 (a3 / and~e.0,1,17
:op1 (a4 / activate-01~e.3,12
:ARG0 (p4 / protein~e.24
:name (n6 / name :op1 "b1"~e.7 :op2 "integrin"~e.10)
:quant (s / some~e.6))
:ARG1 (e / enzyme
:name (n3 / name :op1 "tyrosine"~e.14 :op2 "kinase"~e.15 :op3 "Fyn"~e.16))
:mod (a5 / also~e.11))
:op2 (a6 / activate-01~e.12
:ARG0 (p5 / protein~e.24
:name (n2 / name :op1 "b1"~e.7 :op2 "integrin"~e.10)
:quant s)
:ARG1 e
:mod a5)
:ARG0-of (a7 / activate-01~e.3
:ARG1 (p2 / protein~e.24
:name (n5 / name :op1 "Shc"~e.25)
:mod (a8 / adapter~e.23))))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c / cite-01 :ARG2 4~e.27))))
# ::id bel_pmid_1044_6041.20870 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Rac promotes cell cycle progression , an effect that correlates with its ability to organize the cytoskeleton and promote spreading , rather than with its ability to activate MAP kinases ( 63 ) .
# ::alignments 0-1.1.1.1 1-1 2-1.2.1.1 3-1.2.1 4-1.2 7-1.3 9-1.3.1 10-1.3.1.1.r 11-1.3.1.1.1 11-1.3.1.1.1.r 12-1.3.1.1 13-1.3.1.1.2.r 14-1.3.1.1.2.1 16-1.3.1.1.2.1.2 17-1.3.1.1.2 18-1.3.1.1.2.2 19-1.3.1.1.2.2.1 21-1.3.1.1.3 24-1.3.1.1.3.1.1 24-1.3.1.1.3.1.1.r 25-1.3.1.1.3.1 27-1.3.1.1.3.1.2 28-1.3.1.1.3.1.2.2.1.1 29-1.3.1.1.3.1.2.2.1.2 31-1.4.1.1.1
(p / promote-01~e.1
:ARG0 (e / enzyme
:name (n / name :op1 "Rac"~e.0))
:ARG1 (p2 / progress-01~e.4
:ARG1 (c / cycle-02~e.3
:ARG1 (c2 / cell~e.2)))
:ARG2-of (a / affect-01~e.7
:ARG1-of (c3 / correlate-01~e.9
:ARG2~e.10 (c6 / capable-01~e.12
:ARG1~e.11 e~e.11
:ARG2~e.13 (a4 / and~e.17
:op1 (o / organize-01~e.14
:ARG0 e
:ARG1 (c4 / cytoskeleton~e.16))
:op2 (p3 / promote-01~e.18
:ARG1 (s / spread-02~e.19)))
:ARG1-of (i / instead-of-91~e.21
:ARG2 (c7 / capable-01~e.25
:ARG1~e.24 e~e.24
:ARG2 (a3 / activate-01~e.27
:ARG0 e
:ARG1 (p4 / protein-family
:name (n2 / name :op1 "MAP"~e.28 :op2 "kinase"~e.29))))))))
:ARG1-of (d / describe-01
:ARG0 (p5 / publication
:ARG1-of (c5 / cite-01 :ARG2 63~e.31))))
# ::id bel_pmid_1044_6041.21282 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Yes and Lck are known to be enriched in rafts and may mediate the activation of Shc when Fyn is not expressed .
# ::alignments 0-1.1.1.1.1.1.1 2-1.1.1.1.2.1.1 4-1.1 7-1.1.1 8-1.1.1.2.r 9-1.1.1.2 10-1 11-1.2 12-1.2.1 14-1.2.1.2 15-1.2.1.2.1.r 16-1.2.1.2.1.1.1 17-1.2.1.3.r 18-1.2.1.3.2.1.1 20-1.2.1.3.1 20-1.2.1.3.1.r 21-1.2.1.3
(a2 / and~e.10
:op1 (k / know-01~e.4
:ARG1 (e3 / enrich-01~e.7
:ARG1 (a / and
:op1 (e / enzyme
:name (n / name :op1 "Yes"~e.0))
:op2 (e2 / enzyme
:name (n2 / name :op1 "Lck"~e.2)))
:ARG2~e.8 (r / raft~e.9)))
:op2 (p / possible-01~e.11
:ARG1 (m / mediate-01~e.12
:ARG0 a
:ARG1 (a3 / activate-01~e.14
:ARG1~e.15 (p2 / protein
:name (n3 / name :op1 "Shc"~e.16)))
:time~e.17 (e4 / express-03~e.21 :polarity~e.20 -~e.20
:ARG2 (e5 / enzyme
:name (n4 / name :op1 "Fyn"~e.18))))))
# ::id bel_pmid_1044_6041.21342 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Integrin signaling may be needed for the transcription of cyclin D1 , because the cyclin D1 promoter is coordinately regulated by JNK and ERK ( 37 ) ( Fig . 4 ) .
# ::alignments 0-1.2.1.2.1.1.1 1-1.2.1.2 2-1.2 4-1.2.1 5-1.2.1.1.r 7-1.2.1.1 8-1.2.1.1.1.r 9-1.2.1.1.1.1.1 10-1.2.1.1.1.1.2 12-1 14-1.1.2.1 15-1.1.2.1 16-1.1.2 18-1.1.3 19-1.1 20-1.1.1.r 21-1.1.1.1.1.1 22-1.1.1 23-1.1.1.2.1.1 25-1.3.1.1.1 28-1.4.1 30-1.4.1.1
(c / cause-01~e.12
:ARG0 (r / regulate-01~e.19
:ARG0~e.20 (a / and~e.22
:op1 (e2 / enzyme
:name (n4 / name :op1 "JNK"~e.21))
:op2 (e3 / enzyme
:name (n5 / name :op1 "ERK"~e.23)))
:ARG1 (p2 / promote-01~e.16
:ARG1 p~e.14,15)
:manner (c2 / coordinate-01~e.18))
:ARG1 (p4 / possible-01~e.2
:ARG1 (n2 / need-01~e.4
:ARG0~e.5 (t / transcribe-01~e.7
:ARG1~e.8 (p / protein
:name (n3 / name :op1 "cyclin"~e.9 :op2 "D1"~e.10)))
:ARG1 (s / signal-07~e.1
:ARG0 (p5 / protein
:name (n / name :op1 "integrin"~e.0)))))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c3 / cite-01 :ARG2 37~e.25)))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.28 :mod 4~e.30)))
# ::id bel_pmid_1044_6041.21364 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Activated JNK enters the nucleus and phosphorylates the transcription factor c @-@ Jun , which combines with c @-@ Fos to form the AP @-@ 1 transcription factor complex .
# ::alignments 0-1.1.1.2 1-1.1.1.1.1 2-1.1 4-1.1.2 5-1 6-1.2 8-1.2.1 8-1.2.1.2 8-1.2.1.2.r 9-1.2.1.3 10-1.2.1.1.1 12-1.2.1.1.1 15-1.2.1.4 16-1.2.1.4.1.r 17-1.2.1.4.1.1.1 19-1.2.1.4.1.1.1 23-1.2.1.4.2.2.1.1 25-1.2.1.4.2.2.1.1 26-1.2.1.4.2.2 26-1.2.1.4.2.2.2 26-1.2.1.4.2.2.2.r 27-1.2.1.4.2.1 28-1.2.1.4.2
(a / and~e.5
:op1 (e / enter-01~e.2
:ARG0 (e2 / enzyme
:name (n / name :op1 "JNK"~e.1)
:ARG1-of (a2 / activate-01~e.0))
:ARG1 (n2 / nucleus~e.4))
:op2 (p / phosphorylate-01~e.6
:ARG1 (p2 / protein~e.8
:name (n3 / name :op1 "c-Jun"~e.10,12)
:ARG0-of~e.8 (t / transcribe-01~e.8)
:mod (f / factor~e.9)
:ARG1-of (c / combine-01~e.15
:ARG2~e.16 (p3 / protein
:name (n4 / name :op1 "c-Fos"~e.17,19))
:ARG3 (c2 / complex~e.28
:mod (f2 / factor~e.27)
:mod (p4 / protein~e.26
:name (n5 / name :op1 "AP-1"~e.23,25)
:ARG0-of~e.26 (t2 / transcribe-01~e.26)))))
:ARG2 e2))
# ::id bel_pmid_1044_6041.22694 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Several integrins have been found to associate laterally with the oligomeric membrane protein caveolin @-@ 1 , at least in primary cells ( 4 , 5 ) . Although the biochemical nature of this interaction is not known , inhibiting caveolin expression suppresses the formation of focal adhesions and integrin signaling ( 4 , 5 ) .
# ::alignments 0-1.1.1.1.2 1-1.1.1.1.1.1 4-1.1 6-1.1.1 7-1.1.1.3 7-1.1.1.3.r 11-1.1.1.2.2 12-1.1.1.1 12-1.1.1.2 12-1.2.1.1.1 12-1.2.1.2.1.1.2.1 13-1.1.1.2.1.1 15-1.1.1.2.1.1 17-1.1.1.4.2 18-1.1.1.4.2 20-1.1.1.4.1 21-1.1.1.4 23-1.1.2.1.1.1.1 25-1.1.2.1.1.1.2 28-1.2 30-1.2.2.2.1 31-1.2.2.2 32-1.2.2.2.2.r 33-1.2.2.2.2.1 34-1.2.2.2.2 36-1.2.2.1 36-1.2.2.1.r 37-1.2.2 39-1.2.1 40-1.2.1.1.1.1.1 41-1.2.1.1 42-1.2.1.2 44-1.2.1.2.1 45-1.2.1.2.1.1.r 46-1.2.1.2.1.1.1.1 47-1.2.1.2.1.1.1 48-1.2.1.2.1.1 49-1.2.1.2.1.1.2.1.1.1 50-1.2.1.2.1.1.2 52-1.2.3.1.1.1.1 54-1.1.2.1.1.1.2 54-1.2.3.1.1.1.2
(m / multi-sentence
:snt1 (f / find-01~e.4
:ARG1 (a2 / associate-01~e.6
:ARG1 (p6 / protein~e.12
:name (n3 / name :op1 "integrin"~e.1)
:quant (s4 / several~e.0))
:ARG2 (p / protein~e.12
:name (n / name :op1 "caveolin-1"~e.13,15)
:mod (m2 / membrane~e.11
:mod (o / oligomer)))
:manner~e.7 (l / lateral~e.7)
:location (c / cell~e.21
:mod (p2 / primary~e.20)
:mod (a / at-least~e.17,18)))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c2 / cite-01
:ARG2 (a3 / and :op1 4~e.23 :op2 5~e.25,54)))))
:snt2 (h / have-concession-91~e.28
:ARG1 (i3 / inhibit-01~e.39
:ARG1 (e / express-03~e.41
:ARG2 (p5 / protein~e.12
:name (n4 / name :op1 "caveolin"~e.40)))
:ARG0-of (s2 / suppress-01~e.42
:ARG1 (f2 / form-01~e.44
:ARG1~e.45 (a4 / and~e.48
:op1 (a5 / adhere-01~e.47
:mod (f3 / focal~e.46))
:op2 (s3 / signal-07~e.50
:ARG0 (p7 / protein~e.12
:name (n6 / name :op1 "integrin"~e.49)))))))
:ARG2 (k / know-01~e.37 :polarity~e.36 -~e.36
:ARG1 (n2 / nature~e.31
:mod (b / biochemistry~e.30)
:poss~e.32 (i2 / interact-01~e.34
:mod (t / this~e.33))))
:ARG1-of (d2 / describe-01
:ARG0 (p4 / publication
:ARG1-of (c3 / cite-01
:ARG2 (a6 / and :op1 4~e.52 :op2 5~e.54))))))
# ::id bel_pmid_1044_6041.24492 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok IAP , an immunoglobulin superfamily transmembrane protein , cooperates with b3 integrins in binding thrombospondin to cells , and it also activates an inhibitory trimeric guanine nucleotide @- binding protein ( 29 ) .
# ::alignments 0-1.1.1.1.1 3-1.1.1.2.1.1.1 5-1.1.1.3 6-1.1.1 6-1.1.1.2.1 6-1.1.2 8-1.1 10-1.1.2.1.1 11-1.1.2.1.2 13-1.1.3 14-1.1.3.1.1.1 16-1.1.3.2 18-1 19-1.2.1 20-1.2.3 21-1.2 23-1.2.2.3 24-1.2.2.2 25-1.2.2.1.1 26-1.2.2.1.2 28-1.1.3 28-1.2.2.1.2 29-1.1.3.1 29-1.2.2 31-1.3.1.1.1
(a / and~e.18
:op1 (c / cooperate-01~e.8
:ARG0 (p / protein~e.6
:name (n / name :op1 "IAP"~e.0)
:ARG1-of (i4 / include-91
:ARG2 (p2 / protein-family~e.6
:name (n6 / name :op1 "immunoglobulin"~e.3)))
:mod (t / transmembrane~e.5))
:ARG1 (p7 / protein~e.6
:name (n5 / name :op1 "b3"~e.10 :op2 "integrin"~e.11))
:ARG2 (b / bind-01~e.13,28
:ARG1 (p3 / protein~e.29
:name (n2 / name :op1 "thrombospondin"~e.14))
:ARG2 (c2 / cell~e.16)))
:op2 (a2 / activate-01~e.21
:ARG0 p~e.19
:ARG1 (p4 / protein~e.29
:name (n4 / name :op1 "guanine"~e.25 :op2 "nucleotide-binding"~e.26,28)
:mod (t2 / trimeric~e.24)
:ARG0-of (i3 / inhibit-01~e.23))
:mod (a3 / also~e.20))
:ARG1-of (d / describe-01
:ARG0 (p5 / publication
:ARG1-of (c3 / cite-01 :ARG2 29~e.31))))
# ::id bel_pmid_1044_6041.24730 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The FAK and Shc pathways are regulated both positively and negatively by tyrosine phosphatases . Integrin @-@ mediated activation of ERK is suppressed in cells that lack the re @- ceptor @-@ type protein tyrosine phosphatase a or the cytosolic phosphatase SHP @-@ 2 ( 19 ) . These enzymes dephosphorylate the negative regulatory site in Src @-@ family kinases and thus , presumably , amplify both FAK and Shc signaling .
# ::alignments 1-1.3.1.1.1.1.1 2-1.3.1.1 3-1.3.1.1.2.1.1 4-1.2.4.1.1.1.1 4-1.2.4.1.1.2.1 4-1.3.1.1.1 4-1.3.1.1.2 9-1.3.1.1 12-1.3.1.2.1.1 13-1.3.1.2.1.2 15-1.1.1.2.1.1.1 17-1.1.1.2 18-1.1.1 19-1.1.1.1.r 20-1.1.1.1.1.1 22-1.1 23-1.1.2.r 24-1.1.2 26-1.1.2.1 32-1.1.2.1.1.1 32-1.1.2.1.1.1.2 32-1.1.2.1.1.1.2.r 33-1.1.2.1.1.1.1.1 34-1.1.2.1.1.1.1.2 35-1.1.2.1.1.1.1.3 36-1.1.2.1.1.1.1.4 37-1.1.2.1.1 39-1.1.2.1.1.2.2 40-1.1.2.1.1.2 41-1.1.2.1.1.2.1.1 43-1.1.2.1.1.2.1.1 45-1.1.3.1.1.1 48-1.2.2.1 49-1.2.2 50-1.2 52-1.2.1.1 52-1.3.2 53-1.2.1.1 54-1.2.1 55-1.2.3.r 56-1.2.3.1.1.1.1 58-1.2.3.1.1 59-1.2.3 61-1.2.4 63-1.2.4.2 65-1.2.4.1 67-1.2.4.1.1.1.1.1.1 68-1.2.4.1.1 69-1.2.4.1.1.2.1.1.1 70-1.2.4.1.1.1 70-1.2.4.1.1.2
(m / multi-sentence
:snt2 (s / suppress-01~e.22
:ARG1 (a3 / activate-01~e.18
:ARG1~e.19 (e / enzyme
:name (n / name :op1 "ERK"~e.20))
:ARG1-of (m2 / mediate-01~e.17
:ARG0 (p8 / protein
:name (n5 / name :op1 "integrin"~e.15))))
:location~e.23 (c / cell~e.24
:ARG0-of (l / lack-01~e.26
:ARG1 (o / or~e.37
:op1 (e5 / enzyme~e.32
:name (n8 / name :op1 "protein"~e.33 :op2 "tyrosine"~e.34 :op3 "phosphatase"~e.35 :op4 "a"~e.36)
:ARG1-of~e.32 (t / type-03~e.32
:ARG2 (r2 / receptor)))
:op2 (p9 / phosphatase~e.40
:name (n7 / name :op1 "SHP-2"~e.41,43)
:mod (c2 / cytosol~e.39)))))
:ARG1-of (d / describe-01
:ARG0 (p4 / publication
:ARG1-of (c3 / cite-01 :ARG2 19~e.45))))
:snt3 (d2 / dephosphorylate-01~e.50
:ARG1 (s2 / site~e.54
:ARG1-of (d3 / downregulate-01~e.52,53))
:ARG2 (e3 / enzyme~e.49
:mod (t2 / this~e.48))
:ARG3~e.55 (k / kinase~e.59
:ARG1-of (i / include-91
:ARG2 (p3 / protein-family~e.58
:name (n6 / name :op1 "Src"~e.56))))
:ARG0-of (c4 / cause-01~e.61
:ARG1 (a4 / amplify-01~e.65
:ARG1 (a2 / and~e.68
:op1 (s3 / signal-07~e.70
:ARG0 (p6 / pathway~e.4
:name (n9 / name :op1 "FAK"~e.67)))
:op2 (s4 / signal-07~e.70
:ARG0 (p7 / pathway~e.4
:name (n10 / name :op1 "Shc"~e.69)))))
:ARG1-of (p5 / presume-01~e.63)))
:snt1 (a6 / and
:op1 (u / upregulate-01
:ARG1 (a / and~e.2,9
:op1 (p / pathway~e.4
:name (n2 / name :op1 "FAK"~e.1))
:op2 (p2 / pathway~e.4
:name (n3 / name :op1 "Shc"~e.3)))
:ARG2 (e2 / enzyme
:name (n4 / name :op1 "tyrosine"~e.12 :op2 "phosphatase"~e.13)))
:op2 (d4 / downregulate-01~e.52
:ARG1 a
:ARG2 e2)))
# ::id bel_pmid_1044_6041.39480 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Two cytoplasmic protein tyrosine phosphatases , PTP @-@ PEST and PTP @-@ 1B , target p130CAS and may specifically inhibit some of the signals downstream of FAK ( 20 ) .
# ::alignments 0-1.1.1.1 1-1.1.1.3 2-1.1.1.2.1 3-1.1.1.2.2 4-1.1.1.2.3 6-1.1.1.4.1.1.1 6-1.1.1.4.2.1.1 8-1.1.1.4.1.1.1 9-1.1.1.4 10-1.1.1.4.1.1.1 10-1.1.1.4.2.1.1 12-1.1.1.4.2.1.1 14-1.1 15-1.1.2.1.1 16-1 17-1.2 18-1.2.1.2 19-1.2.1 20-1.2.1.1.1.1 23-1.2.1.1 24-1.2.1.1.2.2 26-1.2.1.1.2.1.1.1 28-1.3.1.1.1
(a / and~e.16
:op1 (t / target-01~e.14
:ARG0 (e / enzyme :quant 2~e.0
:name (n / name :op1 "protein"~e.2 :op2 "tyrosine"~e.3 :op3 "phosphatase"~e.4)
:mod (c / cytoplasm~e.1)
:example (a2 / and~e.9
:op1 (e2 / enzyme
:name (n2 / name :op1 "PTP-PEST"~e.6,8,10))
:op2 (e3 / enzyme
:name (n3 / name :op1 "PTP-1B"~e.6,10,12))))
:ARG1 (p / protein
:name (n4 / name :op1 "p130CAS"~e.15)))
:op2 (p2 / possible-01~e.17
:ARG1 (i / inhibit-01~e.19
:ARG1 (s / signal-07~e.23
:ARG2-of (i2 / include-91
:ARG3 (s2 / some~e.20))
:location (r / relative-position
:op1 (p3 / pathway
:name (n5 / name :op1 "FAK"~e.26))
:direction (d2 / downstream~e.24)))
:ARG1-of (s3 / specific-02~e.18)))
:ARG1-of (d3 / describe-01
:ARG0 (p4 / publication
:ARG1-of (c2 / cite-01 :ARG2 20~e.28))))
# ::id bel_pmid_1044_6219.2808 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Stat3 is activated by phosphorylation on Tyr @-@ 705 , which leads to dimer formation , nuclear translocation , and regulation of gene expression .
# ::alignments 0-1.2.1.1 2-1 3-1.1.r 4-1.1 5-1.1.1.r 6-1.1.1.2.1 8-1.1.1.1 11-1.3 12-1.3.1.r 13-1.3.1.1.1.1.1 14-1.3.1.1 16-1.3.1.2.1 17-1.3.1.2 19-1.3.1 20-1.3.1.3 21-1.3.1.3.1.r 22-1.3.1.3.1.1 23-1.3.1.3.1
(a / activate-01~e.2
:ARG0~e.3 (p3 / phosphorylate-01~e.4
:ARG1~e.5 (a2 / amino-acid :mod 705~e.8
:name (n2 / name :op1 "tyrosine"~e.6)))
:ARG1 (p2 / protein
:name (n / name :op1 "Stat3"~e.0))
:ARG0-of (l / lead-03~e.11
:ARG2~e.12 (a3 / and~e.19
:op1 (f / form-01~e.14
:ARG1 (m / macro-molecular-complex
:name (n3 / name :op1 "dimer"~e.13)))
:op2 (t / translocate-01~e.17
:ARG2 (n4 / nucleus~e.16))
:op3 (r / regulate-01~e.20
:ARG1~e.21 (e / express-03~e.23
:ARG2 (g / gene~e.22))))))
# ::id bel_pmid_1044_6219.5996 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Here , we report that Stat3 was specifically associated with PKC delta in vivo in an IL @-@ 6 @-@ dependent manner in several cell types . Furthermore , Stat3 was phosphorylated by PKC delta in vivo on Ser @-@ 727 ,
# ::alignments 0-1.1.3 2-1.1.1 3-1.1 4-1.1.2.r 5-1.1.2.1.1.1 7-1.1.2.3 8-1.1.2 9-1.1.2.2.r 10-1.1.2.2.1.1 11-1.1.2.2.1.2 12-1.1.2.4 13-1.1.2.4 14-1.1.2.4 14-1.1.2.6.r 16-1.1.2.6.1.1.1 18-1.1.2.6.1.1.1 20-1.1.2.6 21-1.1.2.4.r 22-1.1.2.4 22-1.1.2.5.r 23-1.1.2.5.2 24-1.1.2.5.1 25-1.1.2.5 27-1.2 29-1.2.1.1.3.1.1 31-1.2.1 33-1.1.2.2.1.1 34-1.1.2.2.1.2 35-1.1.2.4 35-1.2.1.2.2 36-1.1.2.4 36-1.2.1.2.2 38-1.2.1.1.2.1 40-1.2.1.1.1
(m / multi-sentence
:snt1 (r / report-01~e.3
:ARG0 (w / we~e.2)
:ARG1~e.4 (a / associate-01~e.8
:ARG1 (p / protein
:name (n / name :op1 "Stat3"~e.5))
:ARG2~e.9 (e / enzyme
:name (n2 / name :op1 "PKC"~e.10,33 :op2 "delta"~e.11,34))
:ARG1-of (s / specific-02~e.7)
:manner~e.21 (i / in-vivo~e.12,13,14,22,35,36)
:location~e.22 (t / type-03~e.25
:ARG1 (c / cell~e.24)
:quant (s2 / several~e.23))
:manner~e.14 (d / depend-01~e.20
:ARG1 (p4 / protein
:name (n6 / name :op1 "IL-6"~e.16,18))))
:location (h / here~e.0))
:snt2 (a3 / and~e.27
:op2 (p2 / phosphorylate-01~e.31
:ARG1 (a2 / amino-acid :mod 727~e.40
:name (n5 / name :op1 "serine"~e.38)
:part-of (p3 / protein
:name (n3 / name :op1 "Stat3"~e.29)))
:ARG2 (e2 / enzyme
:name (n4 / name :op1 "PKA" :op2 "delta")
:manner (i2 / in-vivo~e.35,36)))))
# ::id bel_pmid_1044_6219.5998 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Finally , we showed that the phosphorylation of Stat3 by PKC delta led to a negative regulation of Stat3 DNA binding and transcriptional activity .
# ::alignments 0-1.1 0-1.1.r 2-1.2 3-1 4-1.3.r 6-1.3.1 7-1.3.1.1.r 8-1.3.1.1.1.1 9-1.3.1.2.r 10-1.3.1.2.1.1 11-1.3.1.2.1.2 12-1.3 13-1.3.2.r 15-1.3.2.1 16-1.3.2.1 17-1.3.2.1.1.r 18-1.3.2.1.1.1.1 19-1.3.2.1.1.2.1.2.1 20-1.3.2.1.1.2 21-1.3.2 22-1.3.2.2.2 23-1.3.2.2
(s / show-01~e.3 :li~e.0 -1~e.0
:ARG0 (w / we~e.2)
:ARG1~e.4 (l / lead-03~e.12
:ARG0 (p2 / phosphorylate-01~e.6
:ARG1~e.7 (p3 / protein
:name (n / name :op1 "Stat3"~e.8))
:ARG2~e.9 (e / enzyme
:name (n2 / name :op1 "PKC"~e.10 :op2 "delta"~e.11)))
:ARG2~e.13 (a / and~e.21
:op1 (d / downregulate-01~e.15,16
:ARG1~e.17 (p4 / protein
:name (n3 / name :op1 "Stat3"~e.18)
:ARG0-of (b / bind-01~e.20
:ARG1 (n4 / nucleic-acid :wiki "DNA"
:name (n5 / name :op1 "DNA"~e.19)))))
:op2 (a2 / activity-06~e.23
:ARG0 p3
:ARG1 (t / transcribe-01~e.22)))))
# ::id bel_pmid_1044_6219.7272 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Here , we report that Stat3 was specifically associated with PKC delta in vivo in an IL @-@ 6 @-@ dependent manner in several cell types .
# ::alignments 0-1.3 2-1.1 3-1 4-1.2.r 5-1.2.1.1.1 7-1.2.4 8-1.2 9-1.2.2.r 10-1.2.2.1.1 11-1.2.2.1.2 12-1.2.3 13-1.2.3 14-1.2.3 14-1.2.6.r 16-1.2.6.1.1.1 18-1.2.6.1.1.1 20-1.2.6 21-1.2.3.r 22-1.2.3 22-1.2.5.r 23-1.2.5.1.1 24-1.2.5.1 25-1.2.5
(r / report-01~e.3
:ARG0 (w / we~e.2)
:ARG1~e.4 (a / associate-01~e.8
:ARG1 (p / protein
:name (n / name :op1 "Stat3"~e.5))
:ARG2~e.9 (e / enzyme
:name (n2 / name :op1 "PKC"~e.10 :op2 "delta"~e.11))
:manner~e.21 (i / in-vivo~e.12,13,14,22)
:ARG1-of (s / specific-02~e.7)
:location~e.22 (t / type-03~e.25
:ARG1 (c / cell~e.24
:quant (s2 / several~e.23)))
:manner~e.14 (d / depend-01~e.20
:ARG1 (p2 / protein
:name (n3 / name :op1 "IL-6"~e.16,18))))
:location (h / here~e.0))
# ::id bio.chicago_2015.55 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Binding of armadillo to dTCF has been shown to reduce the ability of CBP to catalyze this reaction , perhaps by steric interference [ 97 ] .
# ::alignments 0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.1.1 3-1.1.1.2.r 4-1.1.1.2.1.1 7-1 9-1.1 11-1.1.2 12-1.1.2.1.r 13-1.1.2.1.1.1 15-1.1.2.2 16-1.1.2.2.2.2 17-1.1.2.2.2 17-1.1.2.2.2.1 17-1.1.2.2.2.1.r 19-1.1.2.2.3.2 21-1.1.2.2.3.1 22-1.1.2.2.3 24-1.2.1.1.1
(s / show-01~e.7
:ARG1 (r / reduce-01~e.9
:ARG0 (b / bind-01~e.0
:ARG1~e.1 (p3 / protein
:name (n3 / name :op1 "armadillo"~e.2))
:ARG2~e.3 (p5 / protein
:name (n / name :op1 "dTCF"~e.4)))
:ARG1 (c / capable-01~e.11
:ARG1~e.12 (p4 / protein
:name (n2 / name :op1 "CBP"~e.13))
:ARG2 (c2 / catalyze-01~e.15
:ARG0 p4
:ARG1 (t / thing~e.17
:ARG2-of~e.17 (r2 / react-01~e.17)
:mod (t2 / this~e.16))
:instrument (i / interfere-01~e.22
:mod (s4 / steric~e.21)
:ARG1-of (p / possible-01~e.19)))))
:ARG1-of (d / describe-01
:ARG0 (p2 / publication
:ARG1-of (c3 / cite-01 :ARG2 97~e.24))))
# ::id bio.chicago_2015.119 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In particular , the dCtBP corepressor may interact with Ttk69 to form a repressive complex for transcriptional repression .
# ::alignments 1-1.2 4-1.1.1.1.1 5-1.1.1 6-1 7-1.1 8-1.1.2.r 9-1.1.2.1.1 11-1.1.3 13-1.1.3.2.1 14-1.1.3.2 16-1.1.3.2.1.1 17-1.1.3.2.1
(p / possible-01~e.6
:ARG1 (i / interact-01~e.7
:ARG0 (c / corepressor~e.5
:name (n / name :op1 "dCtBP"~e.4))
:ARG1~e.8 (p4 / protein
:name (n2 / name :op1 "Ttk69"~e.9))
:purpose (f / form-01~e.11
:ARG0 c
:ARG1 (c2 / complex~e.14
:ARG0-of (r / repress-01~e.13,17
:ARG1 (t2 / transcribe-01~e.16)))))
:mod (p2 / particular~e.1))
# ::id bio.chicago_2015.125 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The N @-@ termini of XTcf @-@ 3 and LEF @-@ 1 interact with the Armadillo repeat region of beta @-@ catenin ( Behrens et al. , 1996 ; Huber et al. , 1996 ; Molenaar et al. , 1996 ) .
# ::alignments 1-1.1.1.1.1 1-1.1.2.1.1 3-1.1.1.1.1 3-1.1.2.1.1 5-1.1.1.2.1.1 7-1.1.1.2.1.1 8-1.1 9-1.1.2.2.1.1 11-1.1.2.2.1.1 12-1 13-1.2.r 15-1.2.1.1 16-1.2.1.2 19-1.2.2.1.1 21-1.2.2.1.1 23-1.3.1.1.1.1.1.1 24-1.3.1.1.1 25-1.3.1.1.1.2.1 27-1.3.1.2.2 29-1.3.1.2.1.1.1.1 30-1.3.1 30-1.3.1.1.1 30-1.3.1.2.1 30-1.3.1.3.1 31-1.3.1.1.1.2.1 33-1.3.1.3.2 35-1.3.1.3.1.1.1.1 36-1.3.1 36-1.3.1.1.1 36-1.3.1.2.1 36-1.3.1.3.1 37-1.3.1.1.1.2.1 39-1.3.1.1.2.1
(i / interact-01~e.12
:ARG0 (a / and~e.8
:op1 (p / protein-segment
:name (n / name :op1 "N-terminus"~e.1,3)
:part-of (p13 / protein
:name (n2 / name :op1 "XTcf-3"~e.5,7)))
:op2 (p2 / protein-segment
:name (n3 / name :op1 "N-terminus"~e.1,3)
:part-of (p14 / protein
:name (n4 / name :op1 "LEF-1"~e.9,11))))
:ARG1~e.13 (p9 / protein-segment
:name (n5 / name :op1 "Armadillo"~e.15 :op2 "repeat"~e.16)
:part-of (p3 / protein
:name (n6 / name :op1 "beta-catenin"~e.19,21)))
:ARG1-of (d2 / describe-01
:ARG0 (a3 / and~e.30,36
:op1 (p4 / publication-91
:ARG0 (a2 / and~e.24,30,36
:op1 (p5 / person
:name (n7 / name :op1 "Behrens"~e.23))
:op2 (p6 / person
:mod (o / other~e.25,31,37)))
:time (d3 / date-entity :year 1996~e.39))
:op2 (p7 / publication-91
:ARG0 (a4 / and~e.30,36
:op1 (p8 / person
:name (n8 / name :op1 "Huber"~e.29))
:op2 p6)
:time d3~e.27)
:op3 (p10 / publication-91
:ARG0 (a5 / and~e.30,36
:op1 (p11 / person
:name (n9 / name :op1 "Molenaar"~e.35))
:op2 p6)
:time d3~e.33))))
# ::id bio.chicago_2015.129 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Activation of p53 Sequence @-@ Specific DNA Binding by Acetylation of the p53 C @-@ Terminal Domain .
# ::alignments 0-1 1-1.2.r 2-1.2.1.2.1.1 3-1.2.1.2.1 5-1.2.1 5-1.2.1.2 5-1.2.1.2.r 6-1.2.1.1.1 7-1.2 8-1.1.r 9-1.1 10-1.1.1.r 12-1.1.1.2.1.1 13-1.1.1.1.1 15-1.1.1.1.1 16-1.1.1.1.2
(a / activate-01~e.0
:ARG0~e.8 (a2 / acetylate-01~e.9
:ARG1~e.10 (p3 / protein-segment
:name (n / name :op1 "C-terminus"~e.13,15 :op2 "domain"~e.16)
:part-of (p2 / protein
:name (n3 / name :op1 "p53"~e.12))))
:ARG1~e.1 (b / bind-01~e.7
:ARG1 (n4 / nucleic-acid~e.5
:name (n5 / name :op1 "DNA"~e.6)
:ARG1-of~e.5 (s / specific-02~e.5
:ARG2 (s2 / sequence~e.3
:part-of p2~e.2)))))
# ::id bio.chicago_2015.132 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The nonmodular activation regions contain a TFIID interaction domain that binds specifically to TAFII110 and TAFII250 .
# ::alignments 1-1.1.1 2-1.1.2 3-1.1 4-1 6-1.2.1.1.1.1 7-1.2.1 8-1.2 10-1.2.2 11-1.2.2.2 12-1.2.2.1.r 13-1.2.2.1.1.1.1 14-1.2.2.1 15-1.2.2.1.2.1.1
(c / contain-01~e.4
:ARG0 (r / region~e.3
:mod (n / nonmodular~e.1)
:mod (a / activate-01~e.2))
:ARG1 (d / domain~e.8
:location-of (i / interact-01~e.7
:ARG0 (p / protein
:name (n2 / name :op1 "TFIID"~e.6)))
:ARG1-of (b / bind-01~e.10
:ARG2~e.12 (a2 / and~e.14
:op1 (p2 / protein
:name (n3 / name :op1 "TAFII110"~e.13))
:op2 (p3 / protein
:name (n4 / name :op1 "TAFII250"~e.15)))
:ARG1-of (s / specific-02~e.11))))
# ::id bio.chicago_2015.139 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok ( E ) The TALE motif does not prevent PBX binding to CBP , but changing an arginine to lysine within HD helix 3 increases CBP binding to PBX .
# ::alignments 1-1.3.1.1 4-1.1.2.1.1 5-1.1.2 5-1.2.1.3 7-1.1.1 7-1.1.1.r 8-1.1 9-1.1.3.1.1.1 10-1.1.3 11-1.1.3.2.r 12-1.1.3.2.1.1 14-1 15-1.2.1 17-1.2.1.1.1.1 18-1.2.1.2.r 19-1.2.1.2.1.1 21-1.2.1.3.2.1.1 22-1.2.1.3.1.1 23-1.2.1.3.1.2 24-1.2 25-1.2.2.1 26-1.2.2 27-1.2.2.2.r 28-1.2.2.2
(c / contrast-01~e.14
:ARG1 (p / prevent-01~e.8 :polarity~e.7 -~e.7
:ARG0 (m / motif~e.5
:name (n2 / name :op1 "TALE"~e.4))
:ARG1 (b / bind-01~e.10
:ARG1 (p2 / protein
:name (n3 / name :op1 "PBX"~e.9))
:ARG2~e.11 (p3 / protein
:name (n4 / name :op1 "CBP"~e.12))))
:ARG2 (i / increase-01~e.24
:ARG0 (c2 / change-01~e.15
:ARG1 (a2 / amino-acid
:name (n5 / name :op1 "arginine"~e.17))
:ARG2~e.18 (a3 / amino-acid
:name (n6 / name :op1 "lysine"~e.19))
:location (p4 / protein-segment~e.5
:name (n / name :op1 "helix"~e.22 :op2 3~e.23)
:part-of (p5 / protein
:name (n7 / name :op1 "HD"~e.21))))
:ARG1 (b2 / bind-01~e.26
:ARG1 p3~e.25
:ARG2~e.27 p2~e.28))
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "E"~e.1)))
# ::id bio.chicago_2015.157 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Given that p53 interacts with p300 @/@ CBP ( 3 , 26 , 51 ) , the same membrane was then probed with polyclonal anti @-@ CBP antibodies , which detect both p300 and CBP ( 4 , 56 ) .
# ::alignments 2-1.1.1.1.1 3-1.1 4-1.1.2.r 5-1.1.2.1.1.1 6-1.1.2 7-1.1.2.2.1.1 9-1.3.1.1.1.1 11-1.3.1.1.1.2 13-1.3.1.1.1.3 17-1.2.2.1 18-1.2.2 21-1.2 22-1.2.1.r 23-1.2.1.2 24-1.2.1.1 26-1.2.1.1.1 27-1.2.1 30-1.2.1.3 32-1.1.2.1.1.1 34-1.1.2.2.1.1 36-1.2.1.3.2.1.1.1.1 38-1.2.1.3.2.1.1.1.2
(c / cause-01
:ARG0 (i / interact-01~e.3
:ARG0 (p / protein
:name (n / name :op1 "p53"~e.2))
:ARG1~e.4 (s / slash~e.6
:op1 (p2 / protein
:name (n2 / name :op1 "p300"~e.5,32))
:op2 (p3 / protein
:name (n3 / name :op1 "CBP"~e.7,34))))
:ARG1 (p5 / probe-01~e.21
:ARG0~e.22 (a2 / antibody~e.27
:ARG0-of (o / oppose-01~e.24
:ARG1 p3~e.26)
:mod (p7 / polyclonal~e.23)
:ARG0-of (d2 / detect-01~e.30
:ARG1 (a3 / and
:op1 p2
:op2 p3)
:ARG1-of (d3 / describe-01
:ARG0 (p8 / publication
:ARG1-of (c3 / cite-01
:ARG2 (a4 / and :op1 4~e.36 :op2 56~e.38))))))
:ARG1 (m / membrane~e.18
:ARG1-of (s2 / same-01~e.17)))
:ARG1-of (d / describe-01
:ARG0 (p4 / publication
:ARG1-of (c2 / cite-01
:ARG2 (a / and :op1 3~e.9 :op2 26~e.11 :op3 51~e.13)))))
# ::id bio.chicago_2015.177 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Huckebein , Hairy , Goosecoid , and Engrailed are among the repressors that interact with Groucho ( Paroush et al. 1994 ; Goldstein et al. 1999 ) , whereas Kruppel , Knirps , and Snail interact with dCtBP ( Nibu et al. 1998a ) .
# ::alignments 0-1.1.1.1.1.1 2-1.1.1.2.1.1 4-1.1.1.3.1.1 6-1.1.1 7-1.1.1.4.1.1 9-1.1 11-1.1.2 11-1.1.2.1 11-1.1.2.1.r 13-1.1.2.2 14-1.1.2.2.1.r 15-1.1.2.2.1.1.1 17-1.1.3.1.1.1.1.1.1 18-1.1.3.1.1.1 19-1.1.3.1.1.1.2.1 20-1.1.3.1.1.2.1 22-1.1.3.1.2.1.1.1.1 23-1.1.3.1 23-1.1.3.1.1.1 23-1.1.3.1.2.1 24-1.1.3.1.1.1.2.1 25-1.1.3.1.2.2.1 28-1 29-1.2.1.1.1.1 31-1.2.1.2.1.1 33-1.2.1 34-1.2.1.3.1.1 35-1.2 36-1.2.2.r 37-1.2.2.1.1 39-1.2.3.1.1.1.1.1 40-1.1.3.1 40-1.1.3.1.1.1 40-1.2.3.1.1 41-1.1.3.1.1.1.2.1
(c / contrast-01~e.28
:ARG1 (i2 / include-91~e.9
:ARG1 (a / and~e.6
:op1 (p3 / protein
:name (n2 / name :op1 "Huckebein"~e.0))
:op2 (p4 / protein
:name (n3 / name :op1 "Hairy"~e.2))
:op3 (p18 / protein
:name (n12 / name :op1 "Goosecoid"~e.4))
:op4 (p5 / protein
:name (n4 / name :op1 "Engrailed"~e.7)))
:ARG2 (p / protein~e.11
:ARG0-of~e.11 (r / repress-01~e.11)
:ARG0-of (i / interact-01~e.13
:ARG1~e.14 (p2 / protein
:name (n / name :op1 "Groucho"~e.15))))
:ARG1-of (d4 / describe-01
:ARG0 (a3 / and~e.23,40
:op1 (p6 / publication-91
:ARG0 (a2 / and~e.18,23,40
:op1 (p7 / person
:name (n5 / name :op1 "Paroush"~e.17))
:op2 (p8 / person
:mod (o / other~e.19,24,41)))
:time (d / date-entity :year 1994~e.20))
:op2 (p9 / publication-91
:ARG0 (a4 / and~e.23
:op1 (p10 / person
:name (n6 / name :op1 "Goldstein"~e.22))
:op2 p8)
:time (d2 / date-entity :year 1999~e.25)))))
:ARG2 (i3 / interact-01~e.35
:ARG0 (a5 / and~e.33
:op1 (p12 / protein
:name (n7 / name :op1 "Kruppel"~e.29))
:op2 (p13 / protein
:name (n8 / name :op1 "Knirps"~e.31))
:op3 (p14 / protein
:name (n9 / name :op1 "Snail"~e.34)))
:ARG1~e.36 (p19 / protein
:name (n10 / name :op1 "dCtBP"~e.37))
:ARG1-of (d5 / describe-01
:ARG0 (p15 / publication-91
:ARG0 (a6 / and~e.40
:op1 (p16 / person
:name (n11 / name :op1 "Nibu"~e.39))
:op2 p8)
:time (d3 / date-entity :year 1998)))))
# ::id bio.chicago_2015.218 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok For example , abd @-@ A depends on exd for the regulation of wg , but not for the regulation of dpp [ 14 ] .
# ::alignments 0-1 1-1 3-1.1.1.1.1.1 5-1.1.1.1.1.1 6-1.1.1 6-1.1.2 7-1.1.1.2.r 8-1.1.1.2.1.1 11-1.1.1.3 11-1.1.2.4 13-1.1.1.3.1.1.1 15-1.1 16-1.1.2.1 16-1.1.2.1.r 19-1.1.1.3 20-1.1.2.4.1.r 21-1.1.2.4.1.1.1 23-1.2.1.1.1
(e2 / exemplify-01~e.0,1
:ARG0 (c / contrast-01~e.15
:ARG1 (d / depend-01~e.6
:ARG0 (p2 / protein
:name (n / name :op1 "abd-A"~e.3,5))
:ARG1~e.7 (p3 / protein
:name (n2 / name :op1 "exd"~e.8))
:purpose (r / regulate-01~e.11,19
:ARG1 (p4 / protein
:name (n3 / name :op1 "wg"~e.13))))
:ARG2 (d2 / depend-01~e.6 :polarity~e.16 -~e.16
:ARG0 p2
:ARG1 p3
:purpose (r2 / regulate-01~e.11
:ARG1~e.20 (p5 / protein
:name (n4 / name :op1 "dpp"~e.21)))))
:ARG1-of (d3 / describe-01
:ARG0 (p / publication
:ARG1-of (c2 / cite-01 :ARG2 14~e.23))))
# ::id bio.chicago_2015.232 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok This suggests that Exd is required to release the transcriptional activation function of Dfd independently of Exd enhancement of Dfd @-@ binding affinity on the composite site .
# ::alignments 0-1.1 1-1 2-1.2.r 3-1.2.2.1.1 5-1.2 7-1.2.1 9-1.2.1.2.3 10-1.2.1.2.2 11-1.2.1.2 12-1.2.1.2.1.r 13-1.2.1.2.1.1.1 14-1.2.3.1 16-1.2.3.2.1 17-1.2.3.2 18-1.2.3.2.2.r 19-1.2.3.2.2.1.1 21-1.2.3.2.2.1 22-1.2.3.2.2 23-1.2.3.2.3.r 25-1.2.3.2.3.1 26-1.2.3.2.3
(s / suggest-01~e.1
:ARG0 (t / this~e.0)
:ARG1~e.2 (r / require-01~e.5
:ARG0 (r2 / release-01~e.7
:ARG0 p
:ARG1 (f / function-01~e.11
:ARG0~e.12 (p2 / protein
:name (n2 / name :op1 "Dfd"~e.13))
:ARG1 (a / activate-01~e.10)
:ARG0-of (t3 / transcribe-01~e.9)))
:ARG1 (p / protein
:name (n / name :op1 "Exd"~e.3))
:ARG0-of (d / depend-01 :polarity -~e.14
:ARG1 (e2 / enhance-01~e.17
:ARG0 p~e.16
:ARG1~e.18 (a2 / affinity~e.22
:mod (b / bind-01~e.21
:ARG2 p2~e.19))
:location~e.23 (s2 / site~e.26
:mod (c / composite~e.25))))))
# ::id bio.chicago_2015.289 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Ttk activates ftz transcription in yeast cells
# ::alignments 0-1.1.1.1 1-1 2-1.2.1.1.1 3-1.2 4-1.3.r 5-1.3.1 6-1.3
(a / activate-01~e.1
:ARG0 (e / enzyme
:name (n / name :op1 "Ttk"~e.0))
:ARG1 (t / transcribe-01~e.3
:ARG1 (p / protein
:name (n2 / name :op1 "Ftz"~e.2)))
:location~e.4 (c / cell~e.6
:mod (y / yeast~e.5)))
# ::id bio.chicago_2015.325 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In summary , the genetic analysis of dCtBP mutants suggests that Kruppel , Knirps and Snail depend on dCtBP+ activity , while Hairy and Dorsal continue to function as repressors in the absence of the dCtBP co @-@ repressor .
# ::alignments 1-1 4-1.1.1.1.2 5-1.1.1.1 7-1.1.1.1.1.1.1 7-1.1.1.2.2.1.1.1 8-1.1.1.1.1 8-1.1.1.1.1.2 8-1.1.1.1.1.2.r 9-1.1.1 10-1.1.1.2.r 11-1.1.1.2.1.1.1.1 13-1.1.1.2.1.2.1.1 14-1.1.1.2.1 15-1.1.1.2.1.3.1.1 16-1.1.1.2 19-1.1.1.2.2 21-1.1 22-1.1.2.1.1.1.1.1 23-1.1.2.1.1 24-1.1.2.1.1.2.1.1 25-1.1.2 27-1.1.2.1 28-1.1.2.1.2.r 29-1.1.2.1.2 29-1.1.2.1.2.1 29-1.1.2.1.2.1.r 30-1.1.2.2.r 32-1.1.2.2 33-1.1.2.2.1.r 35-1.1.2.2.1.1.1 38-1.1.2.1.2 38-1.1.2.1.2.1 38-1.1.2.1.2.1.r
(s2 / summarize-01~e.1
:ARG2 (c / contrast-01~e.21
:ARG1 (s3 / suggest-01~e.9
:ARG0 (a / analyze-01~e.5
:ARG1 (p7 / protein~e.8
:name (n / name :op1 "dCtBP"~e.7)
:ARG2-of~e.8 (m / mutate-01~e.8))
:mod (g / genetic~e.4))
:ARG1~e.10 (d / depend-01~e.16
:ARG0 (a2 / and~e.14
:op1 (p2 / protein
:name (n2 / name :op1 "Kruppel"~e.11))
:op2 (p3 / protein
:name (n3 / name :op1 "Knirps"~e.13))
:op3 (p4 / protein
:name (n4 / name :op1 "Snail"~e.15)))
:ARG1 (a3 / activity-06~e.19
:ARG0 (p8 / protein
:name (n5 / name :op1 "dCtBP"~e.7)
:mod (w / wild-type)))))
:ARG2 (c2 / continue-01~e.25
:ARG1 (f / function-01~e.27
:ARG0 (a4 / and~e.23
:op1 (p5 / protein
:name (n6 / name :op1 "Hairy"~e.22))
:op2 (p6 / protein
:name (n7 / name :op1 "Dorsal"~e.24)))
:ARG1~e.28 (m2 / molecular-physical-entity~e.29,38
:ARG0-of~e.29,38 (r / repress-01~e.29,38)))
:condition~e.30 (a5 / absent-01~e.32
:ARG1~e.33 (p / protein
:name (n8 / name :op1 "dCtBP"~e.35)
:ARG0-of (c3 / corepress-00))))))
# ::id bio.chicago_2015.328 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Unilateral photoactivation of UBX repressed ANTP expression on one side of the embryo , indicating that the photo @-@ induced UBX was functional ( Fig . 3C ) .
# ::alignments 0-1.1.3 3-1.1.1.1.1 4-1 5-1.2.1.1.1 6-1.2 7-1.2.2.r 8-1.2.2.1 9-1.2.2 10-1.2.2.2.r 12-1.2.2.2 14-1.3 17-1.1.2 17-1.3.1.1.2.1 19-1.3.1.1.2 20-1.3.1.1.1 22-1.3.1 24-1.4.1 26-1.4.1.1
(r / repress-01~e.4
:ARG0 (a / activate-01
:ARG1 (p2 / protein
:name (n / name :op1 "UBX"~e.3))
:mod (p / photo~e.17)
:mod (u / unilateral~e.0))
:ARG1 (e / express-03~e.6
:ARG2 (p5 / protein
:name (n2 / name :op1 "ANTP"~e.5))
:ARG3~e.7 (s / side~e.9 :quant 1~e.8
:part-of~e.10 (e3 / embryo~e.12)))
:ARG0-of (i / indicate-01~e.14
:ARG1 (f / function-01~e.22
:ARG0 (p3 / protein
:name n~e.20
:ARG2-of (i2 / induce-01~e.19
:ARG0 (p4 / photo~e.17)))))
:ARG1-of (d / describe-01
:ARG0 (f2 / figure~e.24 :mod "3C"~e.26)))
# ::id bio.chicago_2015.340 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Binding of PC and TRX to Ubx , abd @-@ A and Abd @-@ B promoters during different embryonic stages .
# ::alignments 0-1 1-1.1.r 2-1.1.1.1.1 3-1.1 4-1.1.2.1.1 5-1.2.r 6-1.2.1.1.1.1.1 8-1.2.2.1.1.1.1 10-1.2.2.1.1.1.1 11-1.2 12-1.2.2.1.1.1.1 12-1.2.3.1.1.1.1 14-1.2.3.1.1.1.1 15-1.2.1 15-1.2.1.1 15-1.2.1.1.r 15-1.2.2 15-1.2.2.1 15-1.2.2.1.r 15-1.2.3 15-1.2.3.1 15-1.2.3.1.r 16-1.3.r 17-1.3.2 18-1.3.1 19-1.3
(b / bind-01~e.0
:ARG1~e.1 (a / and~e.3
:op1 (p / protein
:name (n / name :op1 "PC"~e.2))
:op2 (p2 / protein
:name (n2 / name :op1 "TRX"~e.4)))
:ARG2~e.5 (a2 / and~e.11
:op1 (m / molecular-physical-entity~e.15
:ARG0-of~e.15 (p3 / promote-01~e.15
:ARG1 (p4 / protein
:name (n3 / name :op1 "Ubx"~e.6))))
:op2 (m2 / molecular-physical-entity~e.15
:ARG0-of~e.15 (p5 / promote-01~e.15
:ARG1 (p6 / protein
:name (n4 / name :op1 "abd-A"~e.8,10,12))))
:op3 (m3 / molecular-physical-entity~e.15
:ARG0-of~e.15 (p7 / promote-01~e.15
:ARG1 (p8 / protein
:name (n5 / name :op1 "Abd-B"~e.12,14)))))
:time~e.16 (s / stage~e.19
:mod (e / embryo~e.18)
:ARG1-of (d / differ-02~e.17)))
# ::id bio.chicago_2015.366 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Su( fu ) regulates Ci via two distinct mechanisms
# ::alignments 3-1 4-1.2.1.1 6-1.3.1 7-1.3.2 8-1.3
(r / regulate-01~e.3
:ARG0 (p / protein
:name (n / name :op1 "Su(fu)"))
:ARG1 (p2 / protein
:name (n2 / name :op1 "Ci"~e.4))
:manner (m / mechanism~e.8 :quant 2~e.6
:mod (d / distinct~e.7)))
# ::id bio.chicago_2015.376 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Thus , the difference between Knirps and other short @-@ range transcriptional repressors may indicate that the mechanism of repression is not identical between these proteins , even though Giant , Knirps , and Kruppel all interact with the CtBP .
# ::alignments 0-1 3-1.1.1.1 5-1.1.1.1.1.1.1 7-1.1.1.1.2.2 8-1.1.1.1.2.3.1 10-1.1.1.1.2.3 11-1.1.1.1.2.1.1 12-1.1.1.1.2 12-1.1.1.1.2.1 12-1.1.1.1.2.1.r 13-1.1 14-1.1.1 15-1.1.1.2.r 17-1.1.1.2.2 17-1.1.1.2.3 19-1.1.1.1.2.1 21-1.1.1.2.1 21-1.1.1.2.1.r 22-1.1.1.2 25-1.1.1.1.1 25-1.1.1.2.4.1.1 25-1.1.1.2.4.1.3 25-1.1.1.2.4.2 27-1.1.1.2.4.r 28-1.1.1.2.4.r 29-1.1.1.2.4.1.1.1.1 31-1.1.1.2.4.1.2 33-1.1.1.2.4.1 34-1.1.1.2.4.1.3.1.1 35-1.1.1.2.4.1.4 36-1.1.1.2.4 39-1.1.1.2.4.2.1.1
(c / cause-01~e.0
:ARG1 (p3 / possible-01~e.13
:ARG1 (i / indicate-01~e.14
:ARG0 (d / differ-02~e.3
:ARG1 (p2 / protein~e.25
:name (n / name :op1 "Knirps"~e.5))
:ARG2 (p / protein~e.12
:ARG0-of~e.12 (r / repress-01~e.12,19
:ARG1 (t / transcribe-01~e.11))
:mod (o / other~e.7)
:mod (r2 / range~e.10
:ARG1-of (s / short-07~e.8))))
:ARG1~e.15 (i2 / identical-01~e.22 :polarity~e.21 -~e.21
:ARG1 (m / mechanism~e.17
:mod r
:poss p2)
:ARG2 (m2 / mechanism~e.17
:mod r
:poss p)
:concession~e.27,28 (i3 / interact-01~e.36
:ARG0 (a / and~e.33
:op1 (p4 / protein~e.25
:name (n2 / name :op1 "Giant"~e.29))
:op2 p2~e.31
:op3 (p6 / protein~e.25
:name (n4 / name :op1 "Kruppel"~e.34))
:mod (a2 / all~e.35))
:ARG1 (p7 / protein~e.25
:name (n5 / name :op1 "CtBP"~e.39)))))))
# ::id bio.chicago_2015.381 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok B @-@ C , dCtBP and Groucho can bind Hairy simultaneously in vitro .
# ::alignments 0-1.1.1.1.1.1 2-1.1.1.1.1.1 4-1.1.1.2.1.1 5-1.1.1 6-1.1.1.3.1.1 7-1 8-1.1 9-1.1.2.1.1 10-1.1.3 11-1.1.4 12-1.1.4
(p / possible-01~e.7
:ARG1 (b / bind-01~e.8
:ARG0 (a / and~e.5
:op1 (p2 / protein
:name (n / name :op1 "B-C"~e.0,2))
:op2 (p3 / protein
:name (n2 / name :op1 "dCtBP"~e.4))
:op3 (p4 / protein
:name (n3 / name :op1 "Groucho"~e.6)))
:ARG1 (p5 / protein
:name (n4 / name :op1 "Hairy"~e.9))
:mod (s / simultaneous~e.10)
:manner (i / in-vitro~e.11,12)))
# ::id bio.chicago_2015.465 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Repression of hth by Antp is cell autonomous .
# ::alignments 0-1 1-1.2.r 2-1.2.1.1 3-1.1.r 4-1.1.1.1 6-1.3.1 7-1.3
(r / repress-01~e.0
:ARG0~e.3 (p2 / protein
:name (n2 / name :op1 "Antp"~e.4))
:ARG1~e.1 (p / protein
:name (n / name :op1 "Hth"~e.2))
:mod (a / autonomous~e.7
:mod (c / cell~e.6)))
# ::id bio.chicago_2015.503 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Whereas , 24B=> Ubx represses both Scr and Antp , leaving abd @-@ A unaffected ( Fig. 4E @-@ H ) .
# ::alignments 0-1 3-1.1.1.2.1.1 4-1.1 6-1.1.2.1.1.1 7-1.1.2 8-1.1.2.2.1.1 10-1.1.1.3 11-1.1.1.3.1.2.1.1 13-1.1.1.3.1.2.1.1 14-1.1.1.3.1 14-1.1.1.3.1.1 14-1.1.1.3.1.1.r 16-1.2.1.1 16-1.2.1.2
(c / contrast-01~e.0
:ARG2 (r / repress-01~e.4
:ARG0 (a3 / and
:op1 (p2 / protein
:name (n6 / name :op1 "24B"))
:op2 (p / protein
:name (n / name :op1 "Ubx"~e.3))
:ARG0-of (l / leave-02~e.10
:ARG1 (a2 / affect-01~e.14 :polarity~e.14 -~e.14
:ARG1 (p5 / protein
:name (n4 / name :op1 "abd-A"~e.11,13)))))
:ARG1 (a / and~e.7
:op1 (p3 / protein
:name (n2 / name :op1 "Scr"~e.6))
:op2 (p4 / protein
:name (n3 / name :op1 "Antp"~e.8))))
:ARG1-of (d / describe-01
:ARG0 (v / value-interval
:op1 (f / figure~e.16 :mod "4A")
:op2 (f2 / figure~e.16 :mod "4H"))))
# ::id bio.chicago_2015.568 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The Ras signaling cascade leads to activation of the inductive transcription factor , Pnt , and inactivation of the Yan repressor .
# ::alignments 1-1.1.1.1.1.1 2-1.1.1 3-1.1 4-1 5-1.2.r 6-1.2.1 9-1.2.1.1.3 10-1.2.1.1.2 11-1.2.1.1 13-1.2.1.1.1.1 15-1.2 16-1.2.1 16-1.2.2 16-1.2.2.1 16-1.2.2.1.r 17-1.2.2.2.r 19-1.2.2.2.1.1.1.1 20-1.2.2.2 20-1.2.2.2.1 20-1.2.2.2.1.r
(l / lead-03~e.4
:ARG0 (c / cascade-01~e.3
:ARG1 (s / signal-07~e.2
:ARG0 (e / enzyme
:name (n2 / name :op1 "Ras"~e.1))))
:ARG2~e.5 (a2 / and~e.15
:op1 (a / activate-01~e.6,16
:ARG1 (f / factor~e.11
:name (n3 / name :op1 "Pnt"~e.13)
:ARG0-of (t / transcribe-01~e.10)
:ARG0-of (i / induce-01~e.9)))
:op2 (a3 / activate-01~e.16 :polarity~e.16 -~e.16
:ARG1~e.17 (p3 / protein~e.20
:ARG0-of~e.20 (r / repress-01~e.20
:ARG1 (p4 / protein
:name (n4 / name :op1 "Yan"~e.19)))))))
# ::id bio.chicago_2015.588 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok H3 was strongly acetylated in the active Abd @-@ B and RpII140 promoters ( Fig. 1a , g; p10 , p10b , pol2 ) , whereas the inactive loci ( iab @-@ 4 , abd @-@ A , Ubx , en , ems and bw ) showed a decrease ( 5 - 10 times lessR than the H3 signal in the active Abd @-@ B and RpII140 promoters ) or absence of acetylation both at the core promoters as well as downstream of the initiator ( Fig. 1b - f , h ) .
# ::alignments 0-1.1.1.1.1 2-1.1.2 3-1.1 6-1.1.3.1.1 6-1.1.3.1.1.2 6-1.1.3.1.1.2.r 7-1.1.3.1.1.1.1 9-1.1.3.1.1.1.1 10-1.1.3.2.1 10-1.1.5.1 11-1.1.4.1.1.1.1 12-1.1.4.1.r 14-1.1.5.1.1 14-1.1.5.1.2 14-1.2.2.1.2 14-1.2.2.1.3 14-1.2.2.1.4 15-1.1.5.1.1.1 18-1.1.3.2.1.1.1 20-1.1.3.2.1.2.1 22-1.1.3.2.1.3.1 25-1 27-1.1.3.1.1 27-1.1.3.1.1.2 27-1.1.3.1.1.2.r 27-1.2.1.1.1.1.1 27-1.2.1.1.1.1.1.1 27-1.2.1.1.1.1.1.1.r 30-1.2.1.1.1.1.2.1.1 32-1.2.1.1.1.1.2.1.1 34-1.2.1.1.1.2.2.1.1 36-1.2.1.1.1.2.2.1.1 38-1.2.1.1.1.3.2.1.1 40-1.2.1.1.1.4.2.1.1 42-1.2.1.1.1.5.2.1.1 43-1.2.1.1.1 44-1.2.1.1.1.6.2.1.1 46-1.2 48-1.2.1.1 50-1.2.1.1.2.1.1.1 52-1.2.1.1.2.1.1.2 53-1.2.1.1.2.1 55-1.2.1.1.2 57-1.2.1.1.2.1.2.1 58-1.2.1.1.2.1.2 61-1.1.3.1.1 61-1.1.3.1.1.2 61-1.1.3.1.1.2.r 62-1.1.3.1.1.1.1 64-1.1.3.1.1.1.1 66-1.1.4.1.1.1.1 67-1.1.4.1.r 69-1.2.1 70-1.2.1.2 71-1.2.1.2.1.r 72-1.2.1.2.1 74-1.2.1.2.2.r 76-1.2.1.2.2.1.2 77-1.1.3 77-1.1.3.1 77-1.1.3.1.r 77-1.1.4 77-1.1.4.1 77-1.2.1.2.2.1 77-1.2.1.2.2.1.1 77-1.2.1.2.2.1.1.r 78-1.2.1.1.2.1.2.2 78-1.2.1.2.2 79-1.2.1.1.2.1.2.2 80-1.2.1.1.2.1.2.2 81-1.2.1.2.2.2.2 82-1.2.1.1.2.1 86-1.2.2.1.1 87-1.2.2.1.1.1
(c / contrast-01~e.25
:ARG1 (a / acetylate-01~e.3
:ARG1 (p5 / protein
:name (n / name :op1 "H3"~e.0))
:ARG1-of (s2 / strong-02~e.2)
:location (m2 / molecular-physical-entity~e.77
:ARG0-of~e.77 (p / promote-01~e.77
:ARG1 (p6 / protein~e.6,27,61
:name (n2 / name :op1 "Abd-B"~e.7,9,62,64)
:ARG0-of~e.6,27,61 (a10 / activity-06~e.6,27,61)))
:ARG1-of (l8 / label-01
:ARG2 (a11 / and~e.10
:op1 (n10 / name :op1 "p10"~e.18)
:op2 (n11 / name :op1 "p10b"~e.20)
:op3 (n12 / name :op1 "pol2"~e.22))))
:location (m / molecular-physical-entity~e.77
:ARG0-of~e.12,67 (p2 / promote-01~e.77
:ARG1 (p7 / protein
:name (n3 / name :op1 "RpII140"~e.11,66))))
:ARG1-of (d / describe-01
:ARG0 (a2 / and~e.10
:op1 (f / figure~e.14 :mod "1a"~e.15)
:op2 (f2 / figure~e.14 :mod "1g"))))
:ARG2 (s3 / show-01~e.46
:ARG1 (o / or~e.69
:op1 (d2 / decrease-01~e.48
:ARG1 (a4 / and~e.43
:op1 (l / locus
:ARG0-of (a3 / activity-06~e.27 :polarity~e.27 -~e.27)
:mod (e / enzyme
:name (n4 / name :op1 "iab-4"~e.30,32)))
:op2 (l2 / locus
:ARG0-of a3
:mod (p9 / protein
:name (n5 / name :op1 "abd-A"~e.34,36)))
:op3 (l3 / locus
:ARG0-of a3
:mod (p10 / protein
:name (n6 / name :op1 "Ubx"~e.38)))
:op4 (l4 / locus
:ARG0-of a3
:mod (p11 / protein
:name (n7 / name :op1 "en"~e.40)))
:op5 (l5 / locus
:ARG0-of a3
:mod (p12 / protein
:name (n8 / name :op1 "ems"~e.42)))
:op6 (l6 / locus
:ARG0-of a3
:mod (p13 / protein
:name (n9 / name :op1 "bw"~e.44))))
:ARG2 (l7 / less-than~e.55
:op1 (p3 / product-of~e.53,82
:op1 (b / between :op1 5~e.50 :op2 10~e.52)
:op2 (s4 / signal-07~e.58
:ARG0 p5~e.57
:location (a5 / and~e.78,79,80
:op1 m2
:op2 m)))))
:op2 (a6 / absent-01~e.70
:ARG1~e.71 (a7 / acetylate-01~e.72)
:ARG2~e.74 (a8 / and~e.78
:op1 (m3 / molecular-physical-entity~e.77
:ARG0-of~e.77 (p4 / promote-01~e.77)
:mod (c2 / core~e.76))
:op2 (r / relative-position
:op1 (m4 / molecular-physical-entity
:ARG0-of (i / initiate-01))
:direction (d3 / downstream~e.81)))))
:ARG1-of (d4 / describe-01
:ARG0 (a9 / and
:op1 (f5 / figure~e.86 :mod "1b"~e.87)
:op2 (f6 / figure~e.14 :mod "1f")
:op3 (f3 / figure~e.14 :mod "1g")
:op4 (f4 / figure~e.14 :mod "1h")))))
# ::id bio.chicago_2015.592 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Since Phyl and Sina associate with the Ttk complex without reducing its apparent size , it indicates that Sina and Phyl bind to Ttk without altering its ability to multimerize .
# ::alignments 0-1 1-1.1.1.1.1.1 2-1.1.1 3-1.1.1.2.1.1 4-1.1 5-1.1.2.r 7-1.1.2.1.1 9-1.1.3.1 9-1.1.3.1.r 10-1.1.3 11-1.1.3.2.1 11-1.1.3.2.1.r 12-1.1.3.2.2 13-1.1.3.2 15-1.2.1 16-1.2 17-1.2.2.r 18-1.2.2.1 19-1.2.2.1 20-1.2.2.1 21-1.2.2 22-1 22-1.2.2.2.r 23-1.2.2.2 24-1.2.2.3.1 24-1.2.2.3.1.r 25-1.2.2.3 26-1.2.2.3.2.1 26-1.2.2.3.2.1.r 27-1.2.2.3.2 28-1.2.2.3.2.2.r 29-1.2.2.3.2.2
(c / cause-01~e.0,22
:ARG0 (a / associate-01~e.4
:ARG1 (a2 / and~e.2
:op1 (p / protein
:name (n / name :op1 "Phyl"~e.1))
:op2 (p2 / protein
:name (n2 / name :op1 "Sina"~e.3)))
:ARG2~e.5 (e / enzyme
:name (n3 / name :op1 "Ttk"~e.7))
:manner (r / reduce-01~e.10 :polarity~e.9 -~e.9
:ARG1 (s / size~e.13
:poss~e.11 e~e.11
:ARG1-of (a3 / appear-02~e.12))))
:ARG1 (i / indicate-01~e.16
:ARG0 a~e.15
:ARG1~e.17 (b / bind-01~e.21
:ARG1 a2~e.18,19,20
:ARG2~e.22 e~e.23
:manner (a4 / alter-01~e.25 :polarity~e.24 -~e.24
:ARG1 (c3 / capable-01~e.27
:ARG1~e.26 e~e.26
:ARG2~e.28 (m / multimerize~e.29))))))
# ::id bio.chicago_2015.596 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In summary , transgenic embryos for wg @-@ Gal4 @/@ UAS @-@ GFP or ems @-@ Gal4 @/@ UAS @-@ GFP accurately reproduce the expression of wg or ems that depends on AbdA or AbdB .
# ::alignments 1-1 3-1.1.1.1 4-1.1.1 5-1.1.1.2.r 6-1.1.1.2.1.1.1 8-1.1.1.2.1.1.1 8-1.1.1.2.2.1.1 10-1.1.1.2.1.1.1 10-1.1.1.2.2.1.1 12-1.1.1.2.1.1.1 12-1.1.1.2.2.1.1 13-1.1.1.2 14-1.1.1.2.2.1.1 16-1.1.1.2.1.1.1 16-1.1.1.2.2.1.1 18-1.1.1.2.1.1.1 18-1.1.1.2.2.1.1 20-1.1.1.2.1.1.1 20-1.1.1.2.2.1.1 21-1.1.3 22-1.1 24-1.1.2 25-1.1.2.1.r 26-1.1.2.1.1.1.1 27-1.1.2.1 28-1.1.2.1.2.1.1 30-1.1.2.2 31-1.1.2.2.1.r 32-1.1.2.2.1.1.1.1 33-1.1.2.2.1 34-1.1.2.2.1.2.1.1
(s2 / summarize-01~e.1
:ARG2 (r / reproduce-01~e.22
:ARG0 (e / embryo~e.4
:mod (t2 / transgenic~e.3)
:poss~e.5 (o / or~e.13
:op1 (o4 / organism
:name (n / name :op1 "wg-Gal4/UAS-GFP"~e.6,8,10,12,16,18,20))
:op2 (o5 / organism
:name (n2 / name :op1 "ems-Gal4/UAS-GFP"~e.8,10,12,14,16,18,20))))
:ARG1 (e4 / express-03~e.24
:ARG2~e.25 (o2 / or~e.27
:op1 (p3 / protein
:name (n3 / name :op1 "wg"~e.26))
:op2 (p4 / protein
:name (n4 / name :op1 "ems"~e.28)))
:ARG0-of (d / depend-01~e.30
:ARG1~e.31 (o3 / or~e.33
:op1 (p / protein
:name (n5 / name :op1 "AbdA"~e.32))
:op2 (p2 / protein
:name (n6 / name :op1 "AbdB"~e.34)))))
:mod (a / accurate~e.21)))
# ::id bio.chicago_2015.627 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Table I dCtBP specifically interacts with Hairy and E ( spl ) mdelta bHLH family members in directed yeast two @-@ hybrid assays ( beta @-@ galactosidase activity in diploid yeast strains )
# ::alignments 0-1.1.2.1 1-1.1.2.1.1 2-1.1.1.1 3-1.3 4-1 5-1.2.r 6-1.2.1.1.1 7-1.2 13-1.2.2.1.1.1.1 14-1.2.2.1.1 15-1.2.2 16-1.4.r 17-1.4.3 18-1.4.2 19-1.4.1.1 21-1.4.1 22-1.4 24-1.5.1.1.1.1 26-1.5.1.1.1.1 27-1.5.1 28-1.5.1.2.r 29-1.5.1.2.1 30-1.5.1.2.2 31-1.5.1.2
(i / interact-01~e.4
:ARG0 (p3 / protein
:name (n / name :op1 "dCtBP"~e.2)
:ARG1-of (d / describe-01
:ARG0 (t / table~e.0 :mod "I"~e.1)))
:ARG1~e.5 (a / and~e.7
:op1 (p / protein
:name (n2 / name :op1 "Hairy"~e.6))
:op2 (m / member~e.15
:ARG1-of (i2 / include-91
:ARG2 (p2 / protein-family~e.14
:name (n3 / name :op1 "E(spl)mdelta-bHLH"~e.13)))))
:ARG1-of (s / specific-02~e.3)
:location~e.16 (a2 / assay-01~e.22
:mod (h / hybrid~e.21 :quant 2~e.19)
:mod (y / yeast~e.18)
:ARG1-of (d3 / direct-01~e.17))
:ARG1-of (m2 / mean-01
:ARG2 (a3 / activity-06~e.27
:ARG0 (e / enzyme
:name (n4 / name :op1 "beta-galactosidase"~e.24,26))
:location~e.28 (s3 / strain~e.31
:mod (d2 / diploid~e.29)
:mod y~e.30))))
# ::id bio.chicago_2015.634 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok dCtBP was identified in interaction studies with Knirps , Snail , and Hairy ( Nibu et al. , 1998b ; Poortinga et al. , 1998 ) These repressor proteins interact with dCtBP through CtBP binding motifs located within the repressor domains located near their C @-@ terminal ends .
# ::alignments 0-1.1.1.1.1 2-1.1 3-1.1.2.r 4-1.1.2.1 5-1.1.2 6-1.1.2.1.1.r 6-1.2.3.r 7-1.1.2.1.1.1.1.1 9-1.1.2.1.1.2.1.1 11-1.1.2.1.1 12-1.1.2.1.1.3.1.1 14-1.1.3.1.1.1.1.1.1 15-1.1.3.1.1.1 16-1.1.3.1.1.1.2.1 20-1.1.3.1.2.1.1.1.1 21-1.1.3.1 21-1.1.3.1.1.1 21-1.1.3.1.2.1 22-1.1.3.1.1.1.2.1 24-1.1.3.1.1.2.1 26-1.2.1.2 27-1.2.1 27-1.2.1.1 27-1.2.1.1.r 28-1.2.1 29-1.2 30-1.2.3.r 31-1.1.1.1.1 33-1.2.3.1.1.1.1 34-1.2.3.1 35-1.2.3 36-1.2.3.2.r 39-1.2.3.2.2 40-1.2.3.2 41-1.2.3.2.r 42-1.2.3.2.1 43-1.2.3.2.1.1.1 43-1.2.3.2.1.1.1.r 44-1.2.3.2.1.1.2.1.1 46-1.2.3.2.1.1.2.1.1 47-1.2.3.2.1.1
(m / multi-sentence
:snt1 (i / identify-01~e.2
:ARG1 (p13 / protein
:name (n / name :op1 "dCtBP"~e.0,31))
:location~e.3 (s2 / study-01~e.5
:ARG1 (i2 / interact-01~e.4
:ARG0~e.6 (a / and~e.11
:op1 (p2 / protein
:name (n2 / name :op1 "Knirps"~e.7))
:op2 (p3 / protein
:name (n3 / name :op1 "Snail"~e.9))
:op3 (p4 / protein
:name (n4 / name :op1 "Hairy"~e.12)))))
:ARG1-of (d2 / describe-01
:ARG0 (a2 / and~e.21
:op1 (p5 / publication-91
:ARG0 (a3 / and~e.15,21
:op1 (p6 / person
:name (n5 / name :op1 "Nibu"~e.14))
:op2 (p7 / person
:mod (o / other~e.16,22)))
:time (d / date-entity :year 1998~e.24))
:op2 (p8 / publication-91
:ARG0 (a5 / and~e.21
:op1 (p9 / person
:name (n6 / name :op1 "Poortinga"~e.20))
:op2 p7)
:time d))))
:snt2 (i3 / interact-01~e.29
:ARG0 (p / protein~e.27,28
:ARG0-of~e.27 (r / repress-01~e.27)
:mod (t / this~e.26))
:ARG1 p13
:instrument~e.6,30 (m2 / motif~e.35
:mod (b / bind-01~e.34
:ARG1 (p12 / protein
:name (n8 / name :op1 "CtBP"~e.33)))
:location~e.36,41 (d4 / domain~e.40
:ARG1-of (n9 / near-02~e.42
:ARG2 (e / end~e.47
:poss~e.43 m2~e.43
:mod (p10 / protein-segment
:name (n10 / name :op1 "C-terminus"~e.44,46))))
:part-of p~e.39))))
# ::id bio.chicago_2015.635 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok ( E ) Association of Sina with HA @-@ tagged Ttk is specifically enhanced by Phyl .
# ::alignments 1-1.4.1.1 3-1.2 4-1.2.1.r 5-1.2.1.1.1 6-1.2.2.r 7-1.2.2.2.1.1.1 9-1.2.2.2 10-1.2.2.1.1 12-1.3 13-1 14-1.1.r 15-1.1.1.1
(e / enhance-01~e.13
:ARG0~e.14 (p / protein
:name (n3 / name :op1 "Phyl"~e.15))
:ARG1 (a / associate-01~e.3
:ARG1~e.4 (p2 / protein
:name (n / name :op1 "Sina"~e.5))
:ARG2~e.6 (e2 / enzyme
:name (n2 / name :op1 "Ttk"~e.10)
:ARG1-of (t / tag-01~e.9
:ARG2 (p4 / protein
:name (n4 / name :op1 "HA"~e.7)))))
:ARG1-of (s / specific-02~e.12)
:ARG1-of (d / describe-01
:ARG0 (f / figure :mod "E"~e.1)))
# ::id bio.chicago_2015.679 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In the bug Oncopeltus fasciatus , Dfd cannot activate pb because pb is not even present in the maxillae ( 30 ) .
# ::alignments 2-1.4.2 3-1.4.1.1 4-1.4.1.2 6-1.2.1.1.1 7-1 7-1.1 7-1.1.r 8-1.2 9-1.2.2.1.1 10-1.3 11-1.3.1.2 13-1.3.1.1 13-1.3.1.1.r 14-1.3.1.4 15-1.3.1
(p2 / possible-01~e.7 :polarity~e.7 -~e.7
:ARG1 (a / activate-01~e.8
:ARG0 (p / protein
:name (n / name :op1 "Dfd"~e.6))
:ARG1 (e / enzyme
:name (n2 / name :op1 "pb"~e.9)))
:ARG1-of (c / cause-01~e.10
:ARG0 (p3 / present-02~e.15 :polarity~e.13 -~e.13
:ARG1 e~e.11
:ARG2 (m / maxilla)
:mod (e2 / even~e.14)))
:location (o / organism
:name (n3 / name :op1 "Oncopeltus"~e.3 :op2 "fasciatus"~e.4)
:mod (b / bug~e.2)))
# ::id bio.chicago_2015.705 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We have also tested if Trl and PcG genes interact to silence the endogenous Ubx gene and MCP reporter constructs in double heterozygous animals .
# ::alignments 0-1.1 2-1.3 3-1 5-1.2.2.1.1 6-1.2.4.1 7-1.2.3.1.1 8-1.2.2 8-1.2.3 9-1.2 11-1.2.4 13-1.2.4.2.1.1.2 14-1.2.4.2.1.1.1.1 15-1.2.4.2.1.1 15-1.2.4.2.2.1 16-1.2.4.2 17-1.2.4.2.2.1.1.1 18-1.2.4.2.2.1.2 19-1.2.4.2.1 19-1.2.4.2.2 20-1.2.4.3.r 21-1.2.4.3.1.1 22-1.2.4.3.1 23-1.2.4.3
(t / test-01~e.3
:ARG0 (w / we~e.0)
:ARG1 (i / interact-01~e.9 :mode interrogative
:ARG0 (g / gene~e.8
:name (n / name :op1 "Trl"~e.5))
:ARG1 (g2 / gene~e.8
:name (n2 / name :op1 "PcG"~e.7))
:purpose (s / silence-01~e.11
:ARG0 (a / and~e.6
:op1 g
:op2 g2)
:ARG1 (a2 / and~e.16
:op1 (c / construct-01~e.19
:ARG1 (g3 / gene~e.15
:name (n3 / name :op1 "Ubx"~e.14)
:mod (e / endogenous~e.13)))
:op2 (c2 / construct-01~e.19
:ARG1 (g4 / gene~e.15
:name (n4 / name :op1 "MCP"~e.17)
:ARG0-of (r / report-01~e.18))))
:location~e.20 (a3 / animal~e.23
:mod (h2 / heterozygous~e.22
:mod (d / double~e.21)))))
:mod (a4 / also~e.2))
# ::id bio.chicago_2015.708 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In these studies , Gro was found to interact specifically with Hairy and Hairy @-@ related proteins , and maternally expressed Gro was shown to be required for the transcriptional repression of genes that direct Drosophila segmentation , neurogenesis , and sex @-@ determination -- three processes known to be regulated by Hairy family repressors .
# ::alignments 1-1.1.2.1 2-1.1.2 4-1.1.1.1.1.1 6-1.1 8-1.1.1 9-1.1.1.3 10-1.1.1.2.r 11-1.1.1.2.1.1.1 12-1.1.1.2 13-1.1.1.2.1.1.1 15-1.1.1.2.2.1 16-1.1.1.2.2 18-1 18-1.1.1.2 19-1.2.1.2.2.1.1.1 20-1.2.1.2.2 21-1.2.1.2.1.1 23-1.2 26-1.2.1 27-1.2.1.1.r 29-1.2.1.1.2 30-1.2.1.1 31-1.2.1.1.1.r 32-1.2.1.1.1 34-1.2.1.1.1.1 35-1.2.1.1.1.1.1.1.1.1.1 36-1.2.1.1.1.1.1.1 38-1.2.1.1.1.1.1.2 40-1.2.1.1.1.1.1 41-1.2.1.1.1.1.1.3.1 43-1.2.1.1.1.1.1.3 45-1.2.1.1.1.1.1.4.1.1 46-1.2.1.1.1.1.1.4.1 47-1.2.1.1.1.1.1.4.1.2 50-1.2.1.1.1.1.1.4.1.2.1 51-1.2.1.1.1.1.1.4.1.2.1.1.r 52-1.2.1.1.1.1.1.4.1.2.1.1.1.1 53-1.2.1.1.1.1.1.4.1.2.1.1 54-1.2.1.1.1.1.1.4.1.2.1.1.2
(a2 / and~e.18
:op1 (f / find-01~e.6
:ARG1 (i / interact-01~e.8
:ARG0 (p2 / protein
:name (n / name :op1 "Gro"~e.4))
:ARG1~e.10 (a / and~e.12,18
:op1 (p3 / protein-family
:name (n2 / name :op1 "Hairy"~e.11,13))
:op2 (p4 / protein~e.16
:ARG1-of (r2 / relate-01~e.15
:ARG2 p3)))
:ARG1-of (s / specific-02~e.9))
:location (s2 / study~e.2
:mod (t / this~e.1)))
:op2 (s3 / show-01~e.23
:ARG1 (r3 / require-01~e.26
:ARG0~e.27 (r / repress-01~e.30
:ARG1~e.31 (g / gene~e.32
:ARG0-of (d / direct-01~e.34
:ARG1 (a3 / and~e.40
:op1 (s4 / segment-01~e.36
:ARG1 (o / organism
:name (n3 / name :op1 "Drosophila"~e.35)))
:op2 (n4 / neurogenesis~e.38)
:op3 (d2 / determine-01~e.43
:ARG1 (s5 / sex~e.41))
:ARG1-of (m / mean-01
:ARG2 (p6 / process~e.46 :quant 3~e.45
:ARG1-of (k / know-02~e.47
:ARG3 (r4 / regulate-01~e.50
:ARG0~e.51 (p7 / protein-family~e.53
:name (n5 / name :op1 "Hairy"~e.52)
:ARG0-of (r5 / repress-01~e.54))
:ARG1 p6)))))))
:ARG0-of (t2 / transcribe-01~e.29))
:ARG1 (p / protein
:name (n6 / name :op1 "Gro"~e.21)
:ARG2-of (e / express-03~e.20
:ARG3 (o2 / organism
:ARG0-of (h / have-rel-role-91
:ARG2 (m2 / mother~e.19))))))))
# ::id bio.chicago_2015.710 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Recent studies have demonstrated that the Sina and Phyl proteins form a ternary complex with Ttk and promote ubiquitination and rapid degradation of Ttk through the proteasome pathway ( 14 , 22 ) .
# ::alignments 0-1.1.1 1-1.1 3-1 4-1.2.r 6-1.2.1.2.1.1.1 7-1.2.1.2 8-1.2.1.2.2.1.1 9-1.2.1.2.1 9-1.2.1.2.2 10-1.2.1 12-1.2.1.1.1 13-1.2.1.1 14-1.2.1.2.r 14-1.2.3.r 15-1.2.1.2.3.1.1 16-1.2 16-1.2.2.1 17-1.2.2 18-1.2.2.2.1 19-1.2.2.2 20-1.2.2.2.2.2 21-1.2.2.2.2 22-1.2.2.2.2.1.r 23-1.2.2.2.2.1 26-1.2.3.1.1 27-1.2.3 29-1.3.1.1.1.1 31-1.3.1.1.1.2
(d / demonstrate-01~e.3
:ARG0 (s / study~e.1
:time (r / recent~e.0))
:ARG1~e.4 (a2 / and~e.16
:op1 (f / form-01~e.10
:ARG1 (c / complex~e.13
:mod (t / ternary~e.12))
:ARG2~e.14 (a / and~e.7
:op1 (p / protein~e.9
:name (n / name :op1 "Sina"~e.6))
:op2 (p2 / protein~e.9
:name (n2 / name :op1 "Phyl"~e.8))
:op3 (e / enzyme
:name (n3 / name :op1 "Ttk"~e.15))))
:op2 (p3 / promote-01~e.17
:ARG0 (a4 / and~e.16
:op1 p
:op2 p2)
:ARG1 (a3 / and~e.19
:op1 (u / ubiquitinate-01~e.18
:ARG1 e)
:op2 (d2 / degrade-01~e.21
:ARG1~e.22 e~e.23
:mod (r2 / rapid~e.20))))
:instrument~e.14 (p4 / pathway~e.27
:name (n4 / name :op1 "proteasome"~e.26)))
:ARG1-of (d3 / describe-01
:ARG0 (p6 / publication
:ARG1-of (c2 / cite-01
:ARG2 (a5 / and :op1 14~e.29 :op2 22~e.31)))))
# ::id bio.chicago_2015.717 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok If this model is correct , iab @-@ 4 mutations must therefore affect abd @-@ A expression in a specific subset of mesodermal cells which they were not able to identify .
# ::alignments 0-1.2.r 1-1.2.1.1 2-1.2.1 4-1.2 6-1.1.1.1.1 8-1.1.1.1.1 9-1.1.1 9-1.1.1.2 9-1.1.1.2.r 10-1 11-1.1.3 12-1.1 13-1.1.2.1.1.1 15-1.1.2.1.1.1 16-1.1.2 17-1.1.2.2.r 19-1.1.2.2.1 20-1.1.2.2 21-1.1.2.2.2.r 22-1.1.2.2.2.1 23-1.1.2.2.2 25-1.1.2.2.2.2.1 27-1.1.2.2.2.2.2.1 27-1.1.2.2.2.2.2.1.r 28-1.1.2.2.2.2.2 30-1.1.2.2.2.2
(o2 / obligate-01~e.10
:ARG2 (a / affect-01~e.12
:ARG0 (e3 / enzyme~e.9
:name (n2 / name :op1 "iab-4"~e.6,8)
:ARG2-of~e.9 (m2 / mutate-01~e.9))
:ARG1 (e / express-03~e.16
:ARG2 (p2 / protein
:name (n / name :op1 "abd-A"~e.13,15))
:ARG3~e.17 (s / subset~e.20
:ARG1-of (s2 / specific-02~e.19)
:consist-of~e.21 (c / cell~e.23
:mod (m / mesodermal~e.22)
:ARG1-of (i / identify-01~e.30
:ARG0 (t / they~e.25)
:ARG1-of (p / possible-01~e.28 :polarity~e.27 -~e.27)))))
:ARG1-of (c3 / cause-01~e.11))
:condition~e.0 (c2 / correct-02~e.4
:ARG1 (m3 / model~e.2
:mod (t2 / this~e.1))))
# ::id bio.chicago_2015.725 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Dm @-@ Ftz generated strong segmentation phenotypes and interacted strongly with Ftz @-@ F1 , Tc @-@ Ftz caused moderate phenotypes and interacted with Ftz @-@ F1 to a lesser extent than Dm @-@ Ftz , while Sg @-@ Ftz generated extremly weak phenotypes and only interacted marginally with Ftz @-@ F1 .
# ::alignments 0-1.1.1.1.1.1.1 2-1.1.1.1.1.1.1 3-1.1.1.1 4-1.1.1.1.2.1.1 5-1.1.1.1.2.1 6-1.1.1.1.2 7-1.1.1 8-1.1.1.2 9-1.1.1.2.3 11-1.1.1.1.1.1.1 11-1.1.1.2.2.1.1 13-1.1.1.2.2.1.1 15-1.1.2.1.1.1.1 17-1.1.2.1.1.1.1 18-1.1.2.1 19-1.1.2.1.2.1 20-1.1.2.1.2 21-1.1.2 22-1.1.2.2 24-1.1.1.1.1.1.1 24-1.1.1.2.2.1.1 26-1.1.2.2.2 27-1.1.2.1 29-1.1.2.2.3 30-1.1.2.2.3.r 31-1.1.2.2.4.r 32-1.1.2.2.4 34-1.1.1.1.1.1.1 34-1.1.1.2.2.1.1 34-1.2.1.1.1.1 36-1 37-1.2.1.1.1.1 39-1.2.1.1.1.1 40-1.2.1 42-1.2.1.2.1 43-1.2.1.2 44-1.2 45-1.2.2.3.1 46-1.2.2 47-1.2.2.3 49-1.1.1.1.1.1.1 49-1.1.1.2.2.1.1 51-1.1.1.2.2.1.1
(c2 / contrast-01~e.36
:ARG1 (a2 / and
:op1 (a / and~e.7
:op1 (g / generate-01~e.3
:ARG0 (g2 / gene
:name (n / name :op1 "Dm-Ftz"~e.0,2,11,24,34,49))
:ARG1 (p / phenotype~e.6
:mod (s / segment-01~e.5
:ARG1-of (s2 / strong-02~e.4))))
:op2 (i / interact-01~e.8
:ARG0 g2
:ARG1 (g3 / gene
:name (n2 / name :op1 "Ftz-F1"~e.11,13,24,34,49,51))
:ARG1-of s2~e.9))
:op2 (a3 / and~e.21
:op1 (c / cause-01~e.18,27
:ARG0 (g4 / gene
:name (n3 / name :op1 "Tc-Ftz"~e.15,17))
:ARG1 (p2 / phenotype~e.20
:ARG1-of (m / moderate-03~e.19)))
:op2 (i2 / interact-01~e.22
:ARG0 g4
:ARG1 g3~e.26
:extent~e.30 (l / less~e.29)
:compared-to~e.31 g2~e.32)))
:ARG2 (a4 / and~e.44
:op1 (g5 / generate-01~e.40
:ARG0 (g6 / gene
:name (n4 / name :op1 "Sg-Ftz"~e.34,37,39))
:ARG1 (p3 / phenotype~e.43
:ARG1-of (w / weak-02~e.42
:degree (e / extreme))))
:op2 (i3 / interact-01~e.46
:ARG0 g6
:ARG1 g3
:ARG1-of (m2 / marginal-02~e.47
:mod (o / only~e.45)))))
# ::id bio.chicago_2015.734 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Regulation of pb expression by Dfd and Scr
# ::alignments 0-1 1-1.2.r 2-1.2.1.1.1 3-1.2 4-1.1.r 5-1.1.1.1.1 6-1.1 7-1.1.2.1.1
(r / regulate-01~e.0
:ARG0~e.4 (a / and~e.6
:op1 (p / protein
:name (n2 / name :op1 "Dfd"~e.5))
:op2 (p2 / protein
:name (n3 / name :op1 "Scr"~e.7)))
:ARG1~e.1 (e / express-03~e.3
:ARG2 (e2 / enzyme
:name (n / name :op1 "pb"~e.2))))
# ::id bio.chicago_2015.746 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok While iab @-@ 2 , iab @-@ 3 and iab @-@ 4 regulate abd @-@ A in PS7 , PS8 and PS9 respectively , iab @-@ 5 , iab @-@ 6 , iab @-@ 7 and iab @-@ 8 regulate Abd @-@ B expression in PS10 , PS11 , PS12 and PS13 .
# ::alignments 0-1 1-1.1.1.1.1.1 1-1.2.1.1.1.1 3-1.1.1.1.1.1 5-1.1.1.1.1.1 5-1.1.1.2.1.1 5-1.1.1.3.1.1 7-1.1.1.2.1.1 8-1.1.1 9-1.1.1.1.1.1 9-1.1.1.2.1.1 9-1.1.1.3.1.1 11-1.1.1.3.1.1 12-1.1 13-1.1.2.1.1 15-1.1.2.1.1 16-1.1.3.r 17-1.1.3.1.1.1 19-1.1.3.2.1.1 21-1.1.3.3.1.1 24-1.2.1.1.1.1 26-1.2.1.1.1.1 28-1.2.1.1.1.1 28-1.2.1.2.1.1 28-1.2.1.3.1.1 28-1.2.1.4.1.1 30-1.2.1.2.1.1 32-1.2.1.1.1.1 32-1.2.1.2.1.1 32-1.2.1.3.1.1 32-1.2.1.4.1.1 34-1.2.1.3.1.1 35-1.2.1 36-1.2.1.1.1.1 36-1.2.1.2.1.1 36-1.2.1.3.1.1 36-1.2.1.4.1.1 38-1.2.1.4.1.1 39-1.2 40-1.2.2.1.1.1 42-1.2.2.1.1.1 43-1.2.2 44-1.2.3.r 45-1.2.3.1.1.1 47-1.2.3.2.1.1 49-1.2.3.3.1.1 51-1.2.3.4.1.1
(c / contrast-01~e.0
:ARG1 (r / regulate-01~e.12
:ARG0 (a / and~e.8
:op1 (e / enzyme
:name (n / name :op1 "iab-2"~e.1,3,5,9))
:op2 (e2 / enzyme
:name (n2 / name :op1 "iab-3"~e.5,7,9))
:op3 (e3 / enzyme
:name (n3 / name :op1 "iab-4"~e.5,9,11)))
:ARG1 (p / protein
:name (n11 / name :op1 "abd-A"~e.13,15))
:location~e.16 (a2 / and
:op1 (t / thing
:name (n4 / name :op1 "PS7"~e.17))
:op2 (t2 / thing
:name (n5 / name :op1 "PS8"~e.19))
:op3 (t3 / thing
:name (n6 / name :op1 "PS9"~e.21))))
:ARG2 (r2 / regulate-01~e.39
:ARG0 (a3 / and~e.35
:op1 (e4 / enzyme
:name (n7 / name :op1 "iab-5"~e.1,24,26,28,32,36))
:op2 (e5 / enzyme
:name (n8 / name :op1 "iab-6"~e.28,30,32,36))
:op3 (e6 / enzyme
:name (n9 / name :op1 "iab-7"~e.28,32,34,36))
:op4 (e7 / enzyme
:name (n10 / name :op1 "iab-8"~e.28,32,36,38)))
:ARG1 (e9 / express-03~e.43
:ARG2 (p2 / protein
:name (n12 / name :op1 "Abd-B"~e.40,42)))
:location~e.44 (a4 / and
:op1 (t4 / thing
:name (n13 / name :op1 "PS10"~e.45))
:op2 (t5 / thing
:name (n14 / name :op1 "PS11"~e.47))
:op3 (t6 / thing
:name (n15 / name :op1 "PS12"~e.49))
:op4 (t7 / thing
:name (n16 / name :op1 "PS13"~e.51)))))
# ::id bio.chicago_2015.756 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In fact , all PRD=>Hox combinations , except Lab ( data not shown ) and Dfd ( Fig. 3D ) , negatively regulate mesodermal pb expression ( data not shown ) .
# ::alignments 0-1.3 1-1.3 3-1.1.3 5-1.1 7-1.1.3.1 8-1.1.3.1.1.1.1.1 10-1.1.3.1.1.1.2.1 11-1.1.3.1.1.1.2.1.1.1 11-1.1.3.1.1.1.2.1.1.1.r 12-1.1.3.1.1.1.2.1.1 14-1.1.3.1.1 15-1.1.3.1.1.2.1.1 17-1.1.3.1.1.2.2.1 18-1.1.3.1.1.2.2.1.1 21-1 22-1 23-1.2.2 24-1.2.1.1.1 25-1.2 27-1.2.3 28-1.2.3 29-1.2.3
(d4 / downregulate-01~e.21,22
:ARG0 (c / combine-01~e.5
:ARG1 (p / protein
:name (n / name :op1 "PRD"))
:ARG2 (p2 / protein
:name (n2 / name :op1 "Hox"))
:mod (a / all~e.3
:ARG2-of (e / except-01~e.7
:ARG1 (a2 / and~e.14
:op1 (p4 / protein
:name (n3 / name :op1 "Lab"~e.8)
:ARG1-of (d / describe-01
:ARG0 (d2 / data~e.10
:ARG1-of (s / show-01~e.12 :polarity~e.11 -~e.11))))
:op2 (p3 / protein
:name (n4 / name :op1 "Dfd"~e.15)
:ARG1-of (d3 / describe-01
:ARG0 (f / figure~e.17 :mod "3D"~e.18)))))))
:ARG1 (e2 / express-03~e.25
:ARG2 (e3 / enzyme
:name (n5 / name :op1 "pb"~e.24))
:mod (m / mesodermal~e.23)
:ARG1-of d~e.27,28,29)
:mod (i / in-fact~e.0,1))
# ::id bio.chicago_2015.761 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Mutations in dTCF and expression of a dominant @-@ negative dTCF transgene cause a segment polarity phenotype and affect expression of the Wingless target genes engrailed and Ultrabithorax .
# ::alignments 0-1.1.1.1 0-1.1.1.2.1.3 1-1.1.1.1.1.r 2-1.1.1.1.1.1.1 3-1.1.1 4-1.1.1.2 5-1.1.1.2.1.r 7-1.1.1.2.1.2 10-1.1.1.2.1.1.1 11-1.1.1.2.1 12-1.1 14-1.1.2.1 15-1.1.2.2 16-1.1.2 17-1 18-1.2 19-1.2.2 20-1.2.2.1.r 22-1.2.2.1.1.1.1 23-1.2.2.1.1.2 24-1.2.2.1.1 24-1.2.2.1.2 24-1.2.2.1.3 25-1.2.2.1.2.1.1 26-1.2.2.1 27-1.2.2.1.3.1.1
(a2 / and~e.17
:op1 (c / cause-01~e.12
:ARG0 (a / and~e.3
:op1 (m / mutate-01~e.0
:ARG1~e.1 (p / protein
:name (n / name :op1 "dTCF"~e.2)))
:op2 (e / express-03~e.4
:ARG1~e.5 (t / transgene~e.11
:name (n4 / name :op1 "dTCF"~e.10)
:ARG0-of (d / dominate-01~e.7)
:ARG2-of (m2 / mutate-01~e.0 :mod "-/-"))))
:ARG1 (p2 / phenotype~e.16
:mod (s / segment~e.14)
:mod (p3 / polarity~e.15)))
:op2 (a3 / affect-01~e.18
:ARG0 a
:ARG1 (e2 / express-03~e.19
:ARG1~e.20 (a4 / and~e.26
:op1 (g2 / gene~e.24
:name (n3 / name :op1 "Wingless"~e.22)
:ARG1-of (t2 / target-01~e.23))
:op2 (g3 / gene~e.24
:name (n6 / name :op1 "Engrailed"~e.25))
:op3 (g / gene~e.24
:name (n5 / name :op1 "Ultrabithorax"~e.27))))))
# ::id bio.chicago_2015.772 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Treatment with either of the PI 3 @-@ kinase inhibitors , wortmannin or LY294002 , or the MEK inhibitor PD 098059 , which prevents MAPK signaling , attenuated the dexamethasone stimulation of TER without affecting apical junction remodeling .
# ::alignments 0-1.1 1-1.1.1.r 2-1.1.1.1.3 8-1.1.1.1.1.1 9-1.1.1.1 9-1.1.1.1.1 9-1.1.1.1.1.r 11-1.1.1.1.2.1.1.1.1 12-1.1.1.1.2.1 13-1.1.1.1.2.1.2.1.1 15-1.1.1 15-1.1.1.1.2.1 17-1.1.1.2.2.1.1.1 18-1.1.1.2 18-1.1.1.2.2 18-1.1.1.2.2.r 23-1.1.2 24-1.1.2.1.1.1.1 25-1.1.2.1 27-1 29-1.2.1.1.1 30-1.2 31-1.2.2.r 32-1.2.2.1.1 33-1.2.3.1 33-1.2.3.1.r 34-1.2.3 35-1.2.3.2.1.1 36-1.2.3.2.1 37-1.2.3.2
(a / attenuate-01~e.27
:ARG0 (t2 / treat-04~e.0
:ARG2~e.1 (o2 / or~e.15
:op1 (m / molecular-physical-entity~e.9
:ARG0-of~e.9 (i2 / inhibit-01~e.9
:ARG1 (k / kinase~e.8
:name (n3 / name :op1 "PI3")))
:ARG1-of (m2 / mean-01
:ARG2 (o / or~e.12,15
:op1 (s3 / small-molecule
:name (n4 / name :op1 "wortmannin"~e.11))
:op2 (s4 / small-molecule
:name (n5 / name :op1 "LY294002"~e.13))))
:mod (e5 / either~e.2))
:op2 (s6 / small-molecule~e.18
:name (n / name :op1 "PD098059")
:ARG0-of~e.18 (i3 / inhibit-01~e.18
:ARG1 (p / protein-family
:name (n6 / name :op1 "MEK"~e.17)))))
:ARG0-of (p4 / prevent-01~e.23
:ARG1 (s / signal-07~e.25
:ARG0 (p2 / pathway
:name (n2 / name :op1 "MAPK"~e.24)))))
:ARG1 (s2 / stimulate-01~e.30
:ARG0 (s5 / small-molecule
:name (n8 / name :op1 "dexamethasone"~e.29))
:ARG1~e.31 (e4 / enzyme
:name (n7 / name :op1 "TER"~e.32))
:manner (a2 / affect-01~e.34 :polarity~e.33 -~e.33
:ARG1 (r / remodel-01~e.37
:ARG1 (j / junction~e.36
:mod (a3 / apical~e.35))))))
# ::id bio.chicago_2015.777 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The recent finding that the dCtBP protein interacts with the repressors Knirps and Snail ( 14 ) and Hairy ( 17 ) supports this notion .
# ::alignments 1-1.1.3.1 2-1.1.3 5-1.1.1.1.1 6-1.1.1 6-1.1.2.1.1 6-1.1.2.1.2 6-1.1.2.2 7-1.1 8-1.1.2.r 10-1.1.2.3 11-1.1.2.1.1.1.1 12-1.1.2.1 13-1.1.2.1.2.1.1 15-1.1.2.1.3.1.1.1 17-1.1.2 18-1.1.2.2.1.1 20-1.1.2.2.2.1.1.1 22-1 23-1.2.1 24-1.2
(s / support-01~e.22
:ARG0 (i / interact-01~e.7
:ARG0 (p / protein~e.6
:name (n / name :op1 "dCtBP"~e.5))
:ARG1~e.8 (a / and~e.17
:op1 (a2 / and~e.12
:op1 (p2 / protein~e.6
:name (n2 / name :op1 "Knirps"~e.11))
:op2 (p3 / protein~e.6
:name (n3 / name :op1 "Snail"~e.13))
:ARG1-of (d / describe-01
:ARG0 (p4 / publication
:ARG1-of (c / cite-01 :ARG2 14~e.15))))
:op2 (p5 / protein~e.6
:name (n4 / name :op1 "Hairy"~e.18)
:ARG1-of (d2 / describe-01
:ARG0 (p6 / publication
:ARG1-of (c2 / cite-01 :ARG2 17~e.20))))
:ARG0-of (r / repress-01~e.10))
:ARG1-of (f / find-01~e.2
:time (r2 / recent~e.1)))
:ARG1 (n5 / notion~e.24
:mod (t / this~e.23)))
# ::id bio.chicago_2015.798 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Later in development , the transcription patterns in Mcp mutant and yw67 embryos are indistinguishable , suggesting that the Mcp deletion disrupts iab4 transcription only early in development .
# ::alignments 0-1.4 0-1.4.2 0-1.4.2.r 1-1.4.1.r 2-1.4.1 5-1.2.2 6-1.2 7-1.2.1.r 8-1.2.1.1.1.1 9-1.2.1.1 9-1.2.1.1.2 9-1.2.1.1.2.r 10-1.2.1 11-1.2.1.2.1.1 12-1.2.1.2 14-1.1 16-1.3 17-1.3.1.r 19-1.3.1.1.1 20-1.3.1.1 21-1.3.1 22-1.3.1.2.1.1.1 23-1.3.1.2 24-1.3.1.3.2 25-1.3.1.3 26-1.3.1.3.1.r 27-1.3.1.3.1
(d / distinguish-01 :polarity -~e.14
:ARG1 (p / pattern-01~e.6
:ARG1~e.7 (a / and~e.10
:op1 (p2 / protein~e.9
:name (n / name :op1 "Mcp"~e.8)
:ARG2-of~e.9 (m / mutate-01~e.9))
:op2 (e / embryo~e.12
:name (n2 / name :op1 "yw67"~e.11)))
:mod (t / transcribe-01~e.5))
:ARG0-of (s / suggest-01~e.16
:ARG1~e.17 (d2 / disrupt-01~e.21
:ARG0 (d3 / delete-01~e.20
:ARG1 p2~e.19)
:ARG1 (t2 / transcribe-01~e.23
:ARG1 (g / gene
:name (n3 / name :op1 "iab4"~e.22)))
:time (e2 / early~e.25
:op1~e.26 (d4 / develop-01~e.27)
:mod (o / only~e.24))))
:time (l / late~e.0
:op1~e.1 (d5 / develop-01~e.2)
:degree~e.0 (m2 / more~e.0)))
# ::id bio.chicago_2015.807 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We present evidence that Apterous activity depends on the formation of a LIM homeodomain dimer bridged by a dimer of cofactor .
# ::alignments 0-1.1 1-1 2-1.2 2-1.2.1 2-1.2.1.r 3-1.2.1.1.r 4-1.2.1.1.1.1.1.1 5-1.2.1.1.1 6-1.2.1.1 7-1.2.1.1.2.r 9-1.2.1.1.2 10-1.2.1.1.2.1.r 12-1.2.1.1.2.1.1.1.1 13-1.2.1.1.2.1.1.1.2 14-1.2.1.1.2.1 15-1.2.1.1.2.1.2 16-1.2.1.1.2.1.2.1.r 18-1.2.1.1.2.1.2.1 19-1.2.1.1.2.1.2.1.1.r 20-1.2.1.1.2.1.2.1.1
(p / present-01~e.1
:ARG0 (w / we~e.0)
:ARG1 (t / thing~e.2
:ARG0-of~e.2 (e / evidence-01~e.2
:ARG1~e.3 (d / depend-01~e.6
:ARG0 (a / activity-06~e.5
:ARG0 (g / gene
:name (n / name :op1 "Apterous"~e.4)))
:ARG1~e.7 (f / form-01~e.9
:ARG1~e.10 (d2 / dimer~e.14
:mod (p2 / protein-segment
:name (n2 / name :op1 "LIM"~e.12 :op2 "homeodomain"~e.13))
:ARG1-of (b / bridge-01~e.15
:ARG2~e.16 (d3 / dimer~e.18
:mod~e.19 (c / cofactor~e.20)))))))))
# ::id bio.chicago_2015.830 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Brinker is an antagonist of the Dpp @-@ signaling because it prevents the transcription of a subset of Mad activated genes ( Kirkpatrick et al. , 2001 ; Rushlow et al. , 2001 ; Saller and Bienz , 2001 ) , but Brinker is itself a Dpp target ( Minami et al. , 1999 ) because Mad and Schnurri heterodimers can block brk transcription in dpp @-@ responsive cells ( Marty et al. , 2000 ) .
# ::alignments 0-1.1.2.1 1-1.1.2.1.r 3-1.1.2 4-1.1.2.2.r 6-1.1.2.2.1.1.1 8-1.1.2.2 9-1.1 11-1.1.1 13-1.1.1.2 14-1.1.1.2.1.r 16-1.1.1.2.1 18-1.1.1.2.1.1.1.1.1.1.1 19-1.1.1.2.1.1.1.1 20-1.1.1.2.1.1.1 22-1.1.3.1.1.1.1.1.1 23-1.1.3.1.1.1 24-1.1.3.1.1.1.2.1 26-1.1.3.1.2.2 28-1.1.3.1.2.1.1.1.1 29-1.1.3.1 29-1.1.3.1.1.1 29-1.1.3.1.2.1 29-1.1.3.1.3.1 30-1.1.3.1.1.1.2.1 32-1.1.3.1.3.2 34-1.1.3.1.3.1.1.1.1 35-1.1.3.1.3.1 36-1.1.3.1.3.1.2.1.1 38-1.1.3.1.3.2 41-1 42-1.1.1.1.1.1 43-1.1.2.1.r 46-1.2.2.1 47-1.2.2 49-1.2.2.3.1.1.1.1.1 50-1.1.3.1 50-1.1.3.1.1.1 50-1.1.3.1.2.1 50-1.1.3.1.3.1 50-1.2.1.1.1 50-1.2.2.3.1.1 51-1.1.3.1.1.1.2.1 53-1.2.2.3.1.2.1 55-1.2 56-1.2.1.1.1.1 57-1.1.3.1 57-1.1.3.1.1.1 57-1.1.3.1.2.1 57-1.1.3.1.3.1 57-1.2.1.1.1 58-1.2.1.1.1.2.1.1 59-1.2.1.1.1.3 60-1.2.1 61-1.2.1.1 63-1.2.1.1.2 64-1.2.1.2.r 65-1.2.1.2.1.1 67-1.2.1.2.1 68-1.2.1.2 70-1.2.1.3.1.1.1.1.1 71-1.1.3.1 71-1.1.3.1.1.1 71-1.1.3.1.2.1 71-1.1.3.1.3.1 71-1.2.1.3.1.1 72-1.1.3.1.1.1.2.1 74-1.2.1.3.1.2.1
(c / contrast-01~e.41
:ARG1 (c2 / cause-01~e.9
:ARG0 (p / prevent-01~e.11
:ARG0 (p2 / protein
:name (n / name :op1 "brinker"~e.42))
:ARG1 (t / transcribe-01~e.13
:ARG1~e.14 (s / subset~e.16
:ARG2-of (i / include-91
:ARG1 (g / gene~e.20
:ARG1-of (a / activate-01~e.19
:ARG0 (p3 / protein
:name (n2 / name :op1 "Mad"~e.18))))))))
:ARG1 (a2 / antagonist~e.3
:domain~e.1,43 p2~e.0
:topic~e.4 (s2 / signal-07~e.8
:ARG0 (p4 / pathway
:name (n3 / name :op1 "Dpp"~e.6))))
:ARG1-of (d / describe-01
:ARG0 (a3 / and~e.29,50,57,71
:op1 (p5 / publication-91
:ARG0 (a4 / and~e.23,29,50,57,71
:op1 (p6 / person
:name (n4 / name :op1 "Kirkpatrick"~e.22))
:op2 (p7 / person
:mod (o / other~e.24,30,51,72)))
:time (d2 / date-entity :year 2001))
:op2 (p8 / publication-91
:ARG0 (a5 / and~e.29,50,57,71
:op1 (p9 / person
:name (n5 / name :op1 "Rushlow"~e.28))
:op2 p7)
:time d2~e.26)
:op3 (p10 / publication-91
:ARG0 (a6 / and~e.29,35,50,57,71
:op1 (p11 / person
:name (n6 / name :op1 "Saller"~e.34))
:op2 (p12 / person
:name (n7 / name :op1 "Bienz"~e.36)))
:time d2~e.32,38))))
:ARG2 (c3 / cause-01~e.55
:ARG0 (p13 / possible-01~e.60
:ARG1 (b / block-01~e.61
:ARG0 (a7 / and~e.50,57
:op1 p3~e.56
:op2 (p14 / protein
:name (n8 / name :op1 "Schnurri"~e.58))
:mod (h / heterodimer~e.59))
:ARG1 (t2 / transcribe-01~e.63
:ARG1 p2))
:location~e.64 (c4 / cell~e.68
:ARG0-of (r / responsive-02~e.67
:ARG1 p4~e.65))
:ARG1-of (d3 / describe-01
:ARG0 (p15 / publication-91
:ARG0 (a8 / and~e.71
:op1 (p16 / person
:name (n9 / name :op1 "Marty"~e.70))
:op2 p7)
:time (d4 / date-entity :year 2000~e.74))))
:ARG1 (t3 / target-01~e.47
:ARG0 p4~e.46
:ARG1 p2
:ARG1-of (d5 / describe-01
:ARG0 (p17 / publication-91
:ARG0 (a9 / and~e.50
:op1 (p18 / person
:name (n10 / name :op1 "Minami"~e.49))
:op2 p7)
:time (d6 / date-entity :year 1999~e.53))))))
# ::id bio.chicago_2015.858 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok CtBP and Giant exhibited repression activity similar to the Knirps repression domains .
# ::alignments 0-1.1.1.1.1 1-1.1 2-1.1.2.1.1 3-1 4-1.2.2 5-1.2 6-1.2.3 7-1.2.3.1.r 9-1.2.3.1.1.1.1.1 10-1.2.3.1.1 11-1.2.3.1
(e / exhibit-01~e.3
:ARG0 (a / and~e.1
:op1 (p / protein
:name (n / name :op1 "CtBP"~e.0))
:op2 (p2 / protein
:name (n2 / name :op1 "Giant"~e.2)))
:ARG1 (a2 / activity-06~e.5
:ARG0 a
:ARG1 (r / repress-01~e.4
:ARG0 a)
:ARG1-of (r2 / resemble-01~e.6
:ARG2~e.7 (d / domain~e.11
:ARG0-of (r3 / repress-01~e.10
:ARG1 (p3 / protein
:name (n3 / name :op1 "Knirps"~e.9)))))))
# ::id bio.chicago_2015.867 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Pan is bound and its transcriptional activity inhibited by dCBP ( 33 ) .
# ::alignments 0-1.1.1.1.1 2-1.1 3-1 5-1.2.2.2 6-1.2.2 7-1.2 8-1.1.2.r 9-1.1.2.1.1 11-1.3.1.1.1
(a / and~e.3
:op1 (b / bind-01~e.2
:ARG1 (p / protein
:name (n / name :op1 "Pan"~e.0))
:ARG2~e.8 (p2 / protein
:name (n2 / name :op1 "dCBP"~e.9)))
:op2 (i / inhibit-01~e.7
:ARG0 p2
:ARG1 (a2 / activity-06~e.6
:ARG0 p
:ARG1 (t / transcribe-01~e.5
:ARG0 p)))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication-91
:ARG1-of (c / cite-01 :ARG2 33~e.11))))
# ::id bio.chicago_2015.875 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Similarly , ectopic Scr and Dfd proteins have no effect on lab gene expression while we find positive regulation of pb by Dfd and Scr as discussed above .
# ::alignments 0-1.3 2-1.1.2.3 3-1.1.2.1.1.1 4-1.1.2 5-1.1.2.2.1.1 6-1.1.2.1 6-1.1.2.2 8-1.1.1 8-1.1.1.r 9-1.1 10-1.1.3.r 11-1.1.3.1.1 12-1.1.3.1 13-1.1.3 14-1 15-1.2.1 16-1.2 20-1.2.2.2.1.1 22-1.2.2.1 23-1.2.2.1 24-1.2.2.1 25-1.2.3.r 26-1.2.3 27-1.2.3.1
(c / contrast-01~e.14
:ARG1 (a / affect-01~e.9 :polarity~e.8 -~e.8
:ARG0 (a2 / and~e.4
:op1 (p / protein~e.6
:name (n / name :op1 "Scr"~e.3))
:op2 (p2 / protein~e.6
:name (n2 / name :op1 "Dfd"~e.5))
:mod (e / ectopic~e.2))
:ARG1~e.10 (e2 / express-03~e.13
:ARG1 (g / gene~e.12
:mod (l / lab~e.11))))
:ARG2 (f / find-01~e.16
:ARG0 (w / we~e.15)
:ARG1 (u / upregulate-01
:ARG0 a2~e.22,23,24
:ARG1 (e3 / enzyme
:name (n3 / name :op1 "pb"~e.20)))
:ARG1-of~e.25 (d / discuss-01~e.26
:location (a3 / above~e.27)))
:ARG1-of (r / resemble-01~e.0))
# ::id bio.chicago_2015.887 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Impact of CSN @-@ specific phosphorylation on degradation of p53 wt and p53 mutants by the Ub - 26S proteasome system Ub - 26S proteasome @-@ dependent degradation of p53 was studied in reticulocyte lysate containing an intact Ub - 26S proteasome system and the CSN complex .
# ::alignments 0-1.1 1-1.1.1.r 2-1.1.1.1.1.1.1 4-1.1.1.1 5-1.1.1 6-1.1.2.r 7-1.1.2 8-1.1.2.2.r 9-1.1.2.2.1.1.1 9-1.1.2.2.2.1.1 10-1.1.2.2.1.2 11-1.1.2.2 12-1.1.2.2.1.1.1 12-1.1.2.2.2.1.1 13-1.1.2.2.3 14-1.1.2.1.r 16-1.1.2.1.1.1.1 18-1.1.2.1.1.1.1 19-1.1.2.1.1 20-1.1.2.1 21-1.2.1.2.1.1.1 23-1.2.1.2.1.1.1 24-1.2.1.2.1 26-1.2.1.2 27-1.2.1 28-1.2.1.1.r 29-1.2.1.1.1.1 31-1.2 32-1.2.2.r 33-1.2.2.1 34-1.2.2 35-1.2.2.2 37-1.2.2.2.1.1.2 38-1.2.2.2.1.1.1 39-1.2.2.2.1.1.1 40-1.2.2.2.1.1.1 41-1.2.2.2.1.1.1 42-1.2.2.2.1.1 43-1.2.2.2.1 45-1.2.2.2.1.2.1.1 46-1.1.1.1.1 46-1.2.2.2.1.2
(m / multi-sentence
:snt1 (i / impact-01~e.0
:ARG0~e.1 (p / phosphorylate-01~e.5
:ARG1-of (s / specific-02~e.4
:ARG2 (m2 / macro-molecular-complex~e.46
:name (n / name :op1 "CSN"~e.2))))
:ARG1~e.6 (d / degrade-01~e.7
:ARG0~e.14 (s2 / system~e.20
:mod (p2 / proteasome~e.19
:name (n2 / name :op1 "Ub-26S"~e.16,18)))
:ARG1~e.8 (a / and~e.11
:op1 (p3 / protein
:name (n3 / name :op1 "p53"~e.9,12)
:mod (w / wild-type~e.10))
:op2 (p4 / protein
:name (n4 / name :op1 "p53"~e.9,12))
:ARG2-of (m3 / mutate-01~e.13))))
:snt2 (s3 / study-01~e.31
:ARG1 (d2 / degrade-01~e.27
:ARG1~e.28 (p5 / protein
:name (n5 / name :op1 "p53"~e.29))
:ARG0-of (d3 / depend-01~e.26
:ARG1 (p6 / proteasome~e.24
:name (n6 / name :op1 "Ub-26S"~e.21,23))))
:location~e.32 (l / lysate~e.34
:mod (r / reticulocyte~e.33)
:ARG0-of (c4 / contain-01~e.35
:ARG1 (a2 / and~e.43
:op1 (s4 / system~e.42
:mod p6~e.38,39,40,41
:mod (i2 / intact~e.37))
:op2 (m4 / macro-molecular-complex~e.46
:name (n7 / name :op1 "CSN"~e.45)))))))
# ::id bio.chicago_2015.894 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok E6 promotes the ubiquitin @-@ mediated degradation of p53 by the proteasome .
# ::alignments 0-1.1.1.1 1-1 3-1.2.4.1.1.1 5-1.2.4 6-1.2 7-1.2.2.r 8-1.2.2.1.1 9-1.2.3.r 11-1.2.3.1.1
(p / promote-01~e.1
:ARG0 (p2 / protein
:name (n / name :op1 "E6"~e.0))
:ARG1 (d / degrade-01~e.6
:ARG0 p2
:ARG1~e.7 (p3 / protein
:name (n2 / name :op1 "p53"~e.8))
:ARG2~e.9 (m2 / macro-molecular-complex
:name (n4 / name :op1 "proteasome"~e.11))
:ARG1-of (m / mediate-01~e.5
:ARG0 (p5 / protein
:name (n3 / name :op1 "ubiquitin"~e.3)))))
# ::id bio.chicago_2015.900 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The exception to this hierarchy is seen for pb where we find that ectopic epidermal expression of Scr and Dfd actually activate epidermal pb expression ( Fig. 3 ) .
# ::alignments 1-1.1 2-1.1.2.r 3-1.1.2.1 4-1.1.2 6-1 7-1.1.1.r 8-1.1.1.1.1 9-1.1.3.r 10-1.1.3.1 11-1.1.3 12-1.1.3.2.r 13-1.1.3.2.1.2.1 15-1.1.3.2.1 17-1.1.3.2.1.1.1.1.1 18-1.1.3.2.1.1 19-1.1.3.2.1.1.2.1.1 20-1.1.3.2.3 21-1.1.3.2 23-1.1.1.1.1 24-1.1.3.2.1 24-1.1.3.2.2 26-1.2.1 27-1.2.1.1
(s / see-01~e.6
:ARG1 (e / except-01~e.1
:ARG1~e.7 (e7 / enzyme
:name (n / name :op1 "pb"~e.8,23))
:ARG2~e.2 (h / hierarchy~e.4
:mod (t / this~e.3))
:location-of~e.9 (f / find-01~e.11
:ARG0 (w / we~e.10)
:ARG1~e.12 (a / activate-01~e.21
:ARG0 (e2 / express-03~e.15,24
:ARG2 (a2 / and~e.18
:op1 (p2 / protein
:name (n2 / name :op1 "Scr"~e.17))
:op2 (p3 / protein
:name (n3 / name :op1 "Dfd"~e.19)))
:ARG3 (e3 / epidermis
:mod (e4 / ectopic~e.13)))
:ARG1 (e5 / express-03~e.24
:ARG2 e7
:ARG3 (e6 / epidermis))
:ARG1-of (a3 / actual-02~e.20))))
:ARG1-of (d / describe-01
:ARG0 (f2 / figure~e.26 :mod 3~e.27)))
# ::id bio.chicago_2015.901 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok beta @-@ catenin contains amino @- and carboxy @-@ terminal transcriptional activation domains and a covalent fusion of either domain with the amino terminus of LEF @-@ 1 generates a fusion protein that functions constitutively and activates transcription independently of a Wnt signal ( 19 ) . .
# ::alignments 0-1.1.1.1.1 2-1.1.1.1.1 3-1.1 4-1.1.2.1.1.1 6-1.1.2 7-1.1.2.2.1.1 9-1.1.2.1.1.1 9-1.1.2.2.1.1 10-1.1.2.3.1 11-1.1.2.3 13-1.1.2 15-1.2.1.3 16-1.2.1 22-1.2.1.2.1.1 23-1.2.1.2.1.1 25-1.2.1.2.2.1.1 27-1.2.1.2.2.1.1 28-1.2 30-1.2.1 30-1.2.2.1 31-1.2.2 33-1.2.2.2 34-1.2.2.2.1 34-1.2.2.2.1.r 35-1.1.2 36-1.1.2.3 36-1.2.2.3 37-1.2.2.3.1 38-1.2.2.3.2.1 41-1.2.2.3.2.2.1.1.1 42-1.2.2.3.2.2 44-1.3.1.1.1
(a / and
:op1 (c / contain-01~e.3
:ARG0 (p / protein
:name (n / name :op1 "beta-catenin"~e.0,2))
:ARG1 (a2 / and~e.6,13,35
:op1 (p2 / protein-segment
:name (n2 / name :op1 "amino-terminus"~e.4,9))
:op2 (p3 / protein-segment
:name (n3 / name :op1 "carboxy-terminus"~e.7,9))
:ARG0-of (a3 / activate-01~e.11,36
:ARG1 (t / transcribe-01~e.10))))
:op2 (g / generate-01~e.28
:ARG0 (f / fuse-01~e.16,30
:ARG1 (o / or
:op1 p2
:op2 p3)
:ARG2 (p4 / protein-segment
:name (n4 / name :op1 "amino-terminus"~e.22,23)
:part-of (p5 / protein
:name (n5 / name :op1 "LEF-1"~e.25,27)))
:mod (c2 / covalent~e.15))
:ARG1 (p6 / protein~e.31
:ARG3-of (f2 / fuse-01~e.30)
:ARG0-of (f3 / function-01~e.33
:manner~e.34 (c3 / constitutive~e.34))
:ARG0-of (a4 / activate-01~e.36
:ARG1 t~e.37
:ARG0-of (d2 / depend-01 :polarity -~e.38
:ARG1 (s / signal-07~e.42
:ARG0 (p7 / protein
:name (n6 / name :op1 "Wnt"~e.41)))))))
:ARG1-of (d3 / describe-01
:ARG0 (p8 / publication-91
:ARG1-of (c4 / cite-01 :ARG2 19~e.44))))
# ::id bio.chicago_2015.936 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Binding to Mdm2 inhibits the transcriptional activity of p53 ( Momand et al. , 1992 ; Oliner et al. , 1993 ) and promotes the degradation of p53 by the 26S proteasome ( Haupt et al. , 1997 ; Kubbutat et al. , 1997 ; Honda et al. , 1997 ) .
# ::alignments 0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.1.1 3-1.1 5-1.1.2.2 6-1.1.2 7-1.1.2.1.r 8-1.1.2.1.1.1 10-1.1.3.1.1.1.1.1.1 11-1.1.3.1.1.1 12-1.1.3.1.1.1.2.1 14-1.1.3.1.1.2.1 16-1.1.3.1.2.1.1.1.1 17-1.1.3.1 17-1.1.3.1.1.1 17-1.1.3.1.2.1 18-1.1.3.1.1.1.2.1 20-1.1.3.1.2.2.1 22-1 22-1.1.3.1 22-1.1.3.1.1.1 23-1.2 25-1.2.2 26-1.2.2.2.r 27-1.2.2.2 28-1.2.2.1.r 30-1.2.2.1.1.1 31-1.2.2.1 33-1.2.3.1.1.1.1.1.1 34-1 34-1.1.3.1 34-1.1.3.1.1.1 34-1.2.3.1 34-1.2.3.1.1.1 34-1.2.3.1.2.1 34-1.2.3.1.3.1 35-1.1.3.1.1.1.2.1 37-1.2.3.1.2.2 39-1.2.3.1.2.1.1.1.1 40-1 40-1.1.3.1 40-1.1.3.1.1.1 40-1.2.3.1 40-1.2.3.1.1.1 40-1.2.3.1.2.1 40-1.2.3.1.3.1 41-1.1.3.1.1.1.2.1 43-1.2.3.1.3.2 45-1.2.3.1.3.1.1.1.1 46-1 46-1.1.3.1 46-1.1.3.1.1.1 46-1.2.3.1 46-1.2.3.1.1.1 46-1.2.3.1.2.1 46-1.2.3.1.3.1 47-1.1.3.1.1.1.2.1 49-1.2.3.1.1.2.1
(a / and~e.22,34,40,46
:op1 (i / inhibit-01~e.3
:ARG0 (b / bind-01~e.0
:ARG2~e.1 (p / protein
:name (n / name :op1 "Mdm2"~e.2)))
:ARG1 (a2 / activity-06~e.6
:ARG0~e.7 (p2 / protein
:name (n2 / name :op1 "p53"~e.8))
:ARG1 (t / transcribe-01~e.5))
:ARG1-of (d / describe-01
:ARG0 (a3 / and~e.17,22,34,40,46
:op1 (p3 / publication-91
:ARG0 (a4 / and~e.11,17,22,34,40,46
:op1 (p4 / person
:name (n3 / name :op1 "Momand"~e.10))
:op2 (p5 / person
:mod (o / other~e.12,18,35,41,47)))
:time (d2 / date-entity :year 1992~e.14))
:op2 (p6 / publication-91
:ARG0 (a5 / and~e.17
:op1 (p7 / person
:name (n4 / name :op1 "Oliner"~e.16))
:op2 p5)
:time (d3 / date-entity :year 1993~e.20)))))
:op2 (p8 / promote-01~e.23
:ARG0 b
:ARG1 (d4 / degrade-01~e.25
:ARG0~e.28 (p9 / proteasome~e.31
:name (n5 / name :op1 "26S"~e.30))
:ARG1~e.26 p2~e.27)
:ARG1-of (d5 / describe-01
:ARG0 (a6 / and~e.34,40,46
:op1 (p10 / publication-91
:ARG0 (a7 / and~e.34,40,46
:op1 (p11 / person
:name (n6 / name :op1 "Haupt"~e.33))
:op2 p5)
:time (d6 / date-entity :year 1997~e.49))
:op2 (p12 / publication-91
:ARG0 (a8 / and~e.34,40,46
:op1 (p13 / person
:name (n7 / name :op1 "Kubbutat"~e.39))
:op2 p5)
:time d6~e.37)
:op3 (p14 / publication-91
:ARG0 (a9 / and~e.34,40,46
:op1 (p15 / person
:name (n8 / name :op1 "Honda"~e.45))
:op2 p5)
:time d6~e.43)))))
# ::id bio.chicago_2015.970 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Functionally , CBP and p300 enhance CREB @-@ mediated transcription upon PKA activation [ 1,2,4 ] .
# ::alignments 0-1.5 2-1.1.1.1.1 3-1.1 4-1.1.2.1.1 5-1 6-1.2.1.1.1.1 8-1.2.1 9-1.2 11-1.3.1.1.1 12-1.3
(e / enhance-01~e.5
:ARG0 (a / and~e.3
:op1 (p / protein
:name (n / name :op1 "CBP"~e.2))
:op2 (p2 / protein
:name (n2 / name :op1 "p300"~e.4)))
:ARG1 (t / transcribe-01~e.9
:ARG1-of (m / mediate-01~e.8
:ARG0 (p3 / protein
:name (n3 / name :op1 "CREB"~e.6))))
:time (a2 / activate-01~e.12
:ARG0 (e2 / enzyme
:name (n4 / name :op1 "PKA"~e.11)))
:ARG1-of (d / describe-01
:ARG0 (a3 / and
:op1 (p4 / publication
:ARG1-of (c / cite-01
:ARG2 (a4 / and :op1 1 :op2 2 :op3 4)))))
:ARG1-of (f / function-01~e.0))
# ::id bio.chicago_2015.1058 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Purified CREB and CREMalpha proteins were then phosphorylated with PKA .
# ::alignments 0-1.1.3 1-1.1.1.1.1 2-1.1 3-1.1.2.1.1 4-1.1.1 4-1.1.2 6-1.3 7-1 8-1.2.r 9-1.2.1.1
(p / phosphorylate-01~e.7
:ARG1 (a / and~e.2
:op1 (p2 / protein~e.4
:name (n / name :op1 "CREB"~e.1))
:op2 (p3 / protein~e.4
:name (n2 / name :op1 "CREMalpha"~e.3))
:ARG1-of (p4 / purify-01~e.0))
:ARG2~e.8 (e / enzyme
:name (n3 / name :op1 "PKA"~e.9))
:time (t / then~e.6))
# ::id bio.chicago_2015.1064 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Although a mammalian homologue of STE5 has not yet been identified , two proteins , MP1 and JIP @-@ 1 , have been suggested to function as a scaffold for MAPK modules that leads to specific activation of ERK and JNK ( 41 , 52 ) .
# ::alignments 0-1.2.r 2-1.2.2.1 3-1.2.2 4-1.2.2.2.r 5-1.2.2.2.1.1 7-1.2.1 7-1.2.1.r 8-1.2.3 10-1.2 12-1.1.1.1 13-1.1.1 15-1.1.1.2.1.1.1.1 16-1.1.1.2.1 17-1.1.1.2.1.2.1.1 19-1.1.1.2.1.2.1.1 23-1 25-1.1 26-1.1.2.r 26-1.2.3.r 28-1.1.2 29-1.1.3.r 30-1.1.3.1.1.1 31-1.1.3 33-1.1.2.1 34-1.1.2.1.1.r 35-1.1.2.1.1.3 36-1.1.2.1.1 37-1.1.2.1.1.2.r 38-1.1.2.1.1.2.1.1.1 39-1.1.2.1.1.2 40-1.1.2.1.1.2.2.1.1 42-1.3.1.1.1.1 44-1.3.1.1.1.2
(s / suggest-01~e.23
:ARG1 (f / function-01~e.25
:ARG0 (p / protein~e.13 :quant 2~e.12
:ARG1-of (m / mean-01
:ARG2 (a / and~e.16
:op1 (p2 / protein
:name (n / name :op1 "MP1"~e.15))
:op2 (p3 / protein
:name (n2 / name :op1 "JIP-1"~e.17,19)))))
:ARG1~e.26 (s2 / scaffold~e.28
:ARG0-of (l / lead-03~e.33
:ARG2~e.34 (a2 / activate-01~e.36
:ARG0 f
:ARG1~e.37 (a3 / and~e.39
:op1 (e / enzyme
:name (n4 / name :op1 "ERK"~e.38))
:op2 (e2 / enzyme
:name (n5 / name :op1 "JNK"~e.40)))
:ARG1-of (s3 / specific-02~e.35))))
:beneficiary~e.29 (m2 / module~e.31
:mod (p4 / pathway
:name (n3 / name :op1 "MAPK"~e.30))))
:concession~e.0 (i / identify-01~e.10 :polarity~e.7 -~e.7
:ARG1 (h / homologue~e.3
:mod (m3 / mammal~e.2)
:mod~e.4 (p5 / protein
:name (n6 / name :op1 "STE5"~e.5)))
:time~e.26 (y / yet~e.8))
:ARG1-of (d / describe-01
:ARG0 (p6 / publication
:ARG1-of (c / cite-01
:ARG2 (a4 / and :op1 41~e.42 :op2 52~e.44)))))
# ::id bio.chicago_2015.1117 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Since the Asp replacement at Ser greatly decreases , but does not completely block , the activation of CREB by PKA , it is possible that the effect of this mutation is a quantitative rather than a complete block of CREB binding to CBP .
# ::alignments 0-1 3-1.1.1.1 4-1.1.1.1.2.r 5-1.1.1.1.2.1.1 6-1.1.1.3 7-1.1.1 9-1.1 11-1.1.2.1 11-1.1.2.1.r 12-1.1.2.4 13-1.1.2 16-1.1.2.3 17-1.1.2.3.2.r 18-1.1.2.3.2.1.1 19-1.1.2.3.1.r 20-1.1.2.3.1.1.1 24-1.2 27-1.2.1.1.2 33-1.2.1.1.1 34-1.2.1 37-1.1.2.4 38-1.2.1.1 38-1.2.1.2 39-1.2.1 39-1.2.1.2.1.r 40-1.2.1.2.1.1 41-1.2.1.2.1 42-1.2.1.2.1.2.r 43-1.2.1.2.1.2.1.1
(c / cause-01~e.0
:ARG0 (c2 / contrast-01~e.9
:ARG1 (d / decrease-01~e.7
:ARG0 (r / replace-01~e.3
:ARG1 (a / amino-acid
:name (n / name :op1 "aspartic" :op2 "acid"))
:location~e.4 (a2 / amino-acid
:name (n2 / name :op1 "serine"~e.5)))
:ARG1 a3
:ARG2 (g / great~e.6))
:ARG2 (b / block-01~e.13 :polarity~e.11 -~e.11
:ARG0 r
:ARG1 (a3 / activate-01~e.16
:ARG0~e.19 (e / enzyme
:name (n3 / name :op1 "PKA"~e.20))
:ARG1~e.17 (p / protein
:name (n4 / name :op1 "CREB"~e.18)))
:ARG1-of (c3 / complete-01~e.12,37)))
:ARG1 (p2 / possible-01~e.24
:ARG1 (i / instead-of-91~e.34,39
:ARG1 (b2 / block-01~e.38
:mod (q / quantitative~e.33)
:ARG2-of (a4 / affect-01~e.27
:ARG0 r))
:ARG2 (b3 / block-01~e.38
:ARG1~e.39 (b4 / bind-01~e.41
:ARG1 p~e.40
:ARG2~e.42 (p3 / protein
:name (n5 / name :op1 "CBP"~e.43)))
:ARG1-of c3))))
# ::id bio.chicago_2015.1141 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok p300 @/@ CBP interacts with CREB , E1A , PCAF , c @-@ jun , c @-@ fos , c @-@ Myb , MyoD , and TFIIB
# ::alignments 0-1.1.1.1 2-1.1.1.1 3-1 4-1.2.r 5-1.2.1.1.1 7-1.2.2.1.1 9-1.2.3.1.1 11-1.2.4.1.1 11-1.2.5.1.1 11-1.2.6.1.1 13-1.2.4.1.1 15-1.2.4.1.1 15-1.2.5.1.1 15-1.2.6.1.1 17-1.2.5.1.1 19-1.2.4.1.1 19-1.2.5.1.1 19-1.2.6.1.1 21-1.2.6.1.1 23-1.2.7.1.1 25-1.2 26-1.2.8.1.1
(i / interact-01~e.3
:ARG0 (p / protein-family
:name (n / name :op1 "p300/CBP"~e.0,2))
:ARG1~e.4 (a / and~e.25
:op1 (p2 / protein
:name (n2 / name :op1 "CREB"~e.5))
:op2 (p3 / protein
:name (n3 / name :op1 "E1A"~e.7))
:op3 (p4 / protein
:name (n4 / name :op1 "PCAF"~e.9))
:op4 (p5 / protein
:name (n5 / name :op1 "c-jun"~e.11,13,15,19))
:op5 (p6 / protein
:name (n6 / name :op1 "c-fos"~e.11,15,17,19))
:op6 (p7 / protein
:name (n7 / name :op1 "c-Myb"~e.11,15,19,21))
:op7 (p8 / protein
:name (n8 / name :op1 "MyoD"~e.23))
:op8 (p9 / protein
:name (n9 / name :op1 "TFIIB"~e.26))))
# ::id bio.chicago_2015.1157 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Somatostatin exerts its antiproliferative effect inhibiting more upstream the TSH stimulation of PKA and PI 3 @-@ kinase , interfering with the TSH @-@ mediated increases of intracellular cAMP levels by inactivation of adenylyl cyclase activity .
# ::alignments 0-1.1.1.1 1-1 2-1.2.1 2-1.2.1.r 3-1.2.2 3-1.2.2.1 3-1.2.2.1.r 4-1.2 5-1.3 6-1.3.3.1 7-1.3.3 9-1.3.2.1.1.1 10-1.3.2 11-1.3.2.2.r 12-1.3.2.2.1.1.1 13-1.3.2.2 17-1.3.2.2.2.1.1 19-1.3.4 20-1.3.4.2.r 22-1.3.4.2.2.1 24-1.3.4.2.2 25-1.3.4.2 26-1.3.4.2.1.r 27-1.3.4.2.1.2 28-1.3.4.2.1.1.1.1 29-1.3.4.2.1 30-1.3.4.3.r 31-1.3.4.3 31-1.3.4.3.1 31-1.3.4.3.1.r 32-1.3.4.3.3.r 33-1.3.4.3.3.1.1.1 34-1.3.4.3.3.1.1.2 35-1.3.4.3.3
(e / exert-01~e.1
:ARG0 (s / small-molecule
:name (n / name :op1 "Somatostatin"~e.0))
:ARG1 (a / affect-01~e.4
:ARG0~e.2 s~e.2
:ARG0-of (c / counter-01~e.3
:ARG1~e.3 (p / proliferate-01~e.3)))
:manner (i / inhibit-01~e.5
:ARG0 s
:ARG1 (s2 / stimulate-01~e.10
:ARG0 (s3 / small-molecule
:name (n2 / name :op1 "TSH"~e.9))
:ARG1~e.11 (a2 / and~e.13
:op1 (e2 / enzyme
:name (n3 / name :op1 "PKA"~e.12))
:op2 (e3 / enzyme
:name (n4 / name :op1 "PI3-kinase"~e.17))))
:location (u / upstream~e.7
:degree (m / more~e.6))
:manner (i2 / interfere-01~e.19
:ARG0 s
:ARG1~e.20 (i3 / increase-01~e.25
:ARG1~e.26 (l / level~e.29
:quant-of (s4 / small-molecule
:name (n5 / name :op1 "cAMP"~e.28))
:mod (i4 / intracellular~e.27))
:ARG1-of (m2 / mediate-01~e.24
:ARG0 s3~e.22))
:manner~e.30 (a3 / activate-01~e.31 :polarity~e.31 -~e.31
:ARG0 s
:ARG1~e.32 (a4 / activity-06~e.35
:ARG0 (e4 / enzyme
:name (n6 / name :op1 "adenylyl"~e.33 :op2 "cyclase"~e.34)))))))
# ::id bio.chicago_2015.1195 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We have previously shown that when the four consensus PKA sites are mutated , CI is no longer proteolyzed , regulated by PKA , or regulated by hedgehog signaling to activate wg ( 7 , 8 ) .
# ::alignments 0-1.1 2-1.3 3-1 5-1.2.5.r 5-1.3.r 7-1.2.5.1.1 8-1.2.5.1.3 9-1.2.5.1.2 10-1.2.5.1 12-1.2.5 14-1.2.1.2.1.1 16-1.2.1.1 16-1.2.1.1.r 16-1.2.2.1 16-1.2.2.1.r 17-1.2.6 17-1.2.6.1 17-1.2.6.1.r 20-1.2.2 22-1.2.2.2.1.1 24-1.2 25-1.2.2 25-1.2.3 26-1.2.3.1.r 27-1.2.3.1.1.1.1 28-1.2.3.1 30-1.2.4 31-1.2.4.2.1.1 33-1.4.1.1.1.1 35-1.4.1.1.1.2
(s / show-01~e.3
:ARG0 (w / we~e.0)
:ARG1 (o / or~e.24
:op1 (p / proteolyze-00 :polarity~e.16 -~e.16
:ARG1 (p2 / protein
:name (n / name :op1 "CI"~e.14)))
:op2 (r / regulate-01~e.20,25 :polarity~e.16 -~e.16
:ARG0 (e / enzyme
:name (n2 / name :op1 "PKA"~e.22))
:ARG1 p2)
:op3 (r2 / regulate-01~e.25
:ARG0~e.26 (s2 / signal-07~e.28
:ARG0 (p3 / protein
:name (n3 / name :op1 "hedgehog"~e.27)))
:ARG1 p2)
:purpose (a / activate-01~e.30
:ARG0 p2
:ARG1 (p4 / protein
:name (n4 / name :op1 "wg"~e.31)))
:time~e.5 (m2 / mutate-01~e.12
:ARG1 (s3 / site-01~e.10 :quant 4~e.7
:ARG1 e~e.9
:mod (c / consensus~e.8)))
:ARG1-of (l / long-03~e.17
:degree~e.17 (m / more~e.17)))
:time~e.5 (p5 / previous~e.2)
:ARG1-of (d / describe-01
:ARG0 (p6 / publication
:ARG1-of (c2 / cite-01
:ARG2 (a2 / and :op1 7~e.33 :op2 8~e.35)))))
# ::id bio.chicago_2015.1205 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok PKA and MAPK lead to the activation of CREB and to the induction of immediate @-@ early genes , one of which--the ubiquitin hydrolase--is neuron specific .
# ::alignments 0-1.1.1.1.1 1-1.1 2-1.1.2.1.1 3-1 4-1.2.r 6-1.2.1 7-1.2.1.2.r 8-1.2.1.2.1.1 12-1.2.2 13-1.2.2.2.r 14-1.2.2.2.1.1 16-1.2.2.2.1 17-1.2.2.2 19-1.2.2.2.2.1.1 22-1.2.2.2.2.1.2.1 24-1.2.2.2.2.1.3.1 25-1.2.2.2.2.1 25-1.2.2.2.2.1.3 25-1.2.2.2.2.1.3.r
(l / lead-03~e.3
:ARG0 (a / and~e.1
:op1 (e / enzyme
:name (n / name :op1 "PKA"~e.0))
:op2 (e2 / enzyme
:name (n2 / name :op1 "MAPK"~e.2)))
:ARG2~e.4 (a2 / and
:op1 (a3 / activate-01~e.6
:ARG0 a
:ARG1~e.7 (p / protein
:name (n3 / name :op1 "CREB"~e.8)))
:op2 (i / induce-01~e.12
:ARG0 a
:ARG2~e.13 (g / gene~e.17
:mod (e3 / early~e.16
:mod (i2 / immediate~e.14))
:ARG2-of (i3 / include-91
:ARG1 (g2 / gene~e.25 :quant 1~e.19
:name (n4 / name :op1 "ubiquitin"~e.22 :op2 "hydrolase")
:ARG1-of~e.25 (s / specific-02~e.25
:ARG2 (n5 / neuron~e.24))))))))
# ::id bio.chicago_2015.1221 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Coexpressing axin inhibited the Lef @-@ 1 reporter activation induced by CKI ( Fig . 3 b ) .
# ::alignments 1-1.1.1.1 2-1 4-1.2.2.1.1 6-1.2.2.1.1 7-1.2.2 7-1.2.2.2 7-1.2.2.2.r 8-1.2 9-1.2.3 10-1.2.1.r 11-1.2.1.1.1 13-1.3.1
(i / inhibit-01~e.2
:ARG0 (p / protein
:name (n / name :op1 "axin"~e.1)
:ARG2-of (c / coexpress-01))
:ARG1 (a / activate-01~e.8
:ARG0~e.10 (e / enzyme
:name (n2 / name :op1 "CKI"~e.11))
:ARG1 (p3 / protein~e.7
:name (n3 / name :op1 "Lef-1"~e.4,6)
:ARG0-of~e.7 (r / report-01~e.7))
:ARG2-of (i2 / induce-01~e.9
:ARG0 e))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.13 :mod "3b")))
# ::id bio.chicago_2015.1253 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Activation of alpha 1A Adrenergic Receptors in Rat1 Cells Does Not Activate MAPK and RSK2-- Other investigators have reported that activation of MAPK ( ERK1 and ERK2 ) by growth factors such as epidermal growth factor can lead to CREB phosphorylation and stimulation of gene expression via CRE elements ( 17 ) .
# ::alignments 0-1.1 2-1.1.2.1.1.1 3-1.1.2.1.1.2 4-1.1.2.1.1.3 5-1.1.2.1.1.4 7-1.1.2.2.1.1 8-1.1.2.2 10-1.1.1 10-1.1.1.r 11-1.1 11-1.1.2 11-1.1.2.r 12-1.1.3.1.1.1 13-1.1.3 15-1.2.1.2 16-1.2.1 16-1.2.1.1 16-1.2.1.1.r 18-1.2 19-1.2.2.r 20-1.2.2.1.1 21-1.2.2.1.1.2.r 22-1.2.2.1.1.2.1.1 24-1.2.2.1.1.2.2.1.1.1.1 25-1.2.2.1.1.2.2.1 26-1.2.2.1.1.2.2.1.2.1.1 28-1.2.2.1.1.1.r 29-1.2.2.1.1.1.1 30-1.2.2.1.1.1 31-1.2.2.1.1.1.2.r 32-1.2.2.1.1.1.2.r 33-1.2.2.1.1.1.2.1.1 34-1.2.2.1.1.1.2.1.2 35-1.2.2.1.1.1.2.1.3 36-1.2.2 37-1.2.2.1 38-1.2.2.1.2.r 39-1.2.2.1.2.1.1.1.1 40-1.2.2.1.2.1 41-1.2.2.1.2 42-1.2.2.1.2.2 43-1.2.2.1.2.2.2.r 44-1.2.2.1.2.2.2.1 45-1.2.2.1.2.2.2 47-1.2.2.1.3.1.1.1 48-1.2.2.1.3 50-1.2.3.1.1.1
(m / multi-sentence
:snt1 (a / activate-01~e.0,11 :polarity~e.10 -~e.10
:ARG0~e.11 (a2 / activate-01~e.11
:ARG1 (p / protein-family
:name (n / name :op1 "alpha"~e.2 :op2 "1A"~e.3 :op3 "adrenergic"~e.4 :op4 "receptor"~e.5))
:location (c / cell~e.8
:name (n2 / name :op1 "Rat1"~e.7)))
:ARG1 (a3 / and~e.13
:op1 (p8 / protein-family
:name (n3 / name :op1 "MAPK"~e.12))
:op2 (e2 / enzyme
:name (n4 / name :op1 "RSK2"))))
:snt2 (r / report-01~e.18
:ARG0 (p2 / person~e.16
:ARG0-of~e.16 (i / investigate-01~e.16)
:mod (o / other~e.15))
:ARG1~e.19 (p3 / possible-01~e.36
:ARG1 (l / lead-03~e.37
:ARG0 (a4 / activate-01~e.20
:ARG0~e.28 (f / factor~e.30
:ARG0-of (g / grow-01~e.29)
:example~e.31,32 (p4 / protein
:name (n5 / name :op1 "epidermal"~e.33 :op2 "growth"~e.34 :op3 "factor"~e.35)))
:ARG1~e.21 (p9 / protein-family
:name (n6 / name :op1 "MAPK"~e.22)
:ARG1-of (m2 / mean-01
:ARG2 (a5 / and~e.25
:op1 (e4 / enzyme
:name (n7 / name :op1 "ERK1"~e.24))
:op2 (e5 / enzyme
:name (n8 / name :op1 "ERK2"~e.26))))))
:ARG2~e.38 (a6 / and~e.41
:op1 (p5 / phosphorylate-01~e.40
:ARG1 (p6 / protein
:name (n9 / name :op1 "CREB"~e.39))
:ARG2 p9)
:op2 (s / stimulate-01~e.42
:ARG0 a4
:ARG1~e.43 (e6 / express-03~e.45
:ARG1 (g2 / gene~e.44))))
:instrument (e7 / element~e.48
:mod (e8 / enzyme
:name (n10 / name :op1 "CRE"~e.47)))))
:ARG1-of (d / describe-01
:ARG0 (p7 / publication
:ARG1-of (c2 / cite-01 :ARG2 17~e.50)))))
# ::id bio.chicago_2015.1255 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok These findings indicate that a PKA @-@ dependent event other than CREB Ser133 phosphorylation is required for Ca2+ induction of CaRE @-@ dependent transcription .
# ::alignments 0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 2-1 3-1.2.r 5-1.2.2.1.1.1.1 7-1.2.2.1 8-1.2.2 9-1.2.2.3 11-1.2.2.2.1.1.3.1.1 13-1.2.2.2.1 15-1.2 18-1.2.1 19-1.2.1.2.r 20-1.2.1.2.1.1.1.1 22-1.2.1.2.1 23-1.2.1.2
(i / indicate-01~e.2
:ARG0 (t / thing~e.1
:ARG1-of~e.1 (f / find-01~e.1)
:mod (t2 / this~e.0))
:ARG1~e.3 (r / require-01~e.15
:ARG0 (i2 / induce-01~e.18
:ARG0 (s / small-molecule
:name (n6 / name :op1 "calcium")
:ARG1-of (i3 / ionize-01 :value "2+"))
:ARG2~e.19 (t3 / transcribe-01~e.23
:ARG0-of (d2 / depend-01~e.22
:ARG1 (s2 / small-molecule
:name (n5 / name :op1 "CaRE"~e.20)))))
:ARG1 (e / event~e.8
:ARG0-of (d / depend-01~e.7
:ARG1 (e2 / enzyme
:name (n / name :op1 "PKA"~e.5)))
:ARG2-of (e3 / except-01
:ARG1 (p / phosphorylate-01~e.13
:ARG1 (a / amino-acid :mod 133
:name (n2 / name :op1 "serine")
:part-of (p2 / protein
:name (n3 / name :op1 "CREB"~e.11)))))
:mod (o / other~e.9))))
# ::id pmid_1592_8660.1 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS ( PMID : 15928660 )
# ::alignments 0-1.1.3 1-1.1.3.1.r 3-1.1.3.1.1.1 4-1.1.3.1 5-1.1.3.r 7-1.1.1 8-1.1 9-1.1.2.r 10-1.1.2.2 11-1.1.2.1.1 12-1 13-1.2.2 14-1.2.3 17-1.2 20-1.2.1.1.1.1 22-1.2.1 24-1.2.1.2.1.1
(h / have-concession-91~e.12
:ARG1 (e / event~e.8
:mod (c / common~e.7)
:location~e.9 (m / medical-condition
:name (n / name :op1 "melanoma"~e.11)
:mod (u / uveal~e.10))
:domain~e.5 (a / activate-01~e.0
:ARG1~e.1 (p / pathway~e.4
:name (n2 / name :op1 "MAPK"~e.3))))
:ARG2 (m2 / mutate-01~e.17
:ARG1 (o2 / or~e.22
:op1 (g / gene
:name (n3 / name :op1 "BRAF"~e.20))
:op2 (g2 / gene
:name (n4 / name :op1 "RAS"~e.24)))
:manner-of e~e.13
:ARG1-of (r / rare-02~e.14))
:ARG1-of (d2 / describe-01
:ARG0 (p2 / publication-91 :ARG8 "PMID15928660")))
# ::id pmid_1592_8660.81 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok RESULTS
# ::alignments 1-1 1-1.1 1-1.1.r
(t / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1))
# ::id pmid_1592_8660.82 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Mutation analysis
# ::alignments 1-1.1 2-1
(a / analyze-01~e.2
:ARG1 (m / mutate-01~e.1))
# ::id pmid_1592_8660.83 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Of the 11 uveal melanoma cell lines under study , only one cell line ( Ocm 1 ) carried a BRAF mutation , the common V599E ( also described by Calipel et al and Kilic et al ) .
# ::alignments 2-1.2.1 3-1.2.2.2 4-1.2.2.1.1 5-1.2 6-1.2 8-1.2.3 10-1.1.3 11-1.1.1 12-1.1 13-1.1 15-1.1.2.1 16-1.1.2.2 18-1.1.4 21-1.1.4.1.2.1.1 23-1.1.4.1 26-1.1.4.1.4 27-1.1.4.1.1 29-1.1.4.1.3.2 30-1.1.4.1.3 31-1.1.4.1.3.1.r 32-1.1.4.1.3.1.1.1.1.1.1 34-1.1.4.1.3.1.1.1 35-1.1.4.1.3.1.1.1.2.1 37-1.1.4.1.3.1 37-1.1.4.1.3.1.1.1 37-1.1.4.1.3.1.2.1 38-1.1.4.1.3.1.2.1.1.1.1 40-1.1.4.1.3.1 40-1.1.4.1.3.1.1.1 40-1.1.4.1.3.1.2.1 41-1.1.4.1.3.1.1.1.2.1
(i / include-91
:ARG1 (c2 / cell-line~e.12,13 :quant 1~e.11
:name (n3 / name :op1 "Ocm"~e.15 :op2 1~e.16)
:mod (o / only~e.10)
:ARG0-of (c3 / carry-01~e.18
:ARG1 (m / mutate-01~e.23 :value "V599E"~e.27
:ARG1 (g / gene
:name (n2 / name :op1 "BRAF"~e.21))
:ARG1-of (d2 / describe-01~e.30
:ARG0~e.31 (a5 / and~e.37,40
:op1 (p / publication-91
:ARG0 (a3 / and~e.34,37,40
:op1 (p2 / person
:name (n4 / name :op1 "Calipel"~e.32))
:op2 (p3 / person
:mod (o2 / other~e.35,41))))
:op2 (p6 / publication-91
:ARG0 (a4 / and~e.37,40
:op1 (p4 / person
:name (n5 / name :op1 "Kilic"~e.38))
:op2 p3)))
:mod (a / also~e.29))
:mod (c4 / common~e.26))))
:ARG2 (c / cell-line~e.5,6 :quant 11~e.2
:mod (m2 / medical-condition
:name (n / name :op1 "melanoma"~e.4)
:mod (u / uveal~e.3))
:ARG1-of (s / study-01~e.8)))
# ::id pmid_1592_8660.84 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok All primary tumour specimens were wild type for BRAF @ .
# ::alignments 0-1.1.2 1-1.1.3 2-1.1.1 3-1.1 4-1.1.r 5-1 6-1 7-1.2.r 9-1.2.1.1
(w / wild-type~e.5,6
:domain~e.4 (s / specimen~e.3
:mod (t / tumor~e.2)
:mod (a / all~e.0)
:mod (p / primary~e.1))
:prep-for~e.7 (g / gene
:name (n / name :op1 "BRAF"~e.9)))
# ::id pmid_1592_8660.85 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok No mutations were found in the NRAS , HRAS or KRAS genes , in both the cell lines and primary tissue .
# ::alignments 0-1.1 0-1.1.r 1-1.2 3-1 7-1.2.1.1.1.1 11-1.2.1.2.1.1 15-1.2.1.3.1.1 17-1.2.1.1 17-1.2.1.2 17-1.2.1.3 22-1.3.1 23-1.3.1 24-1.3 25-1.3.2.1 26-1.3.2
(f / find-01~e.3 :polarity~e.0 -~e.0
:ARG1 (m / mutate-01~e.1
:ARG1 (a / and
:op1 (g / gene~e.17
:name (n / name :op1 "NRAS"~e.7))
:op2 (g2 / gene~e.17
:name (n2 / name :op1 "HRAS"~e.11)
:location a2)
:op3 (g3 / gene~e.17
:name (n3 / name :op1 "KRAS"~e.15)
:location a2)))
:location (a2 / and~e.24
:op1 (c / cell-line~e.22,23)
:op2 (t / tissue~e.26
:mod (p / primary~e.25))))
# ::id pmid_1592_8660.86 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Western blotting
# ::alignments 1-1 2-1
(i / immunoblot-01~e.1,2)
# ::id pmid_1592_8660.87 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In order to assess the level of expression and the activation ( by phosphorylation ) of members of the MAPK pathway downstream of RAS and BRAF , Western blot analysis was performed on uveal melanoma cell lines ( Table 2A ) .
# ::alignments 0-1.1.2.r 1-1.1.2.r 2-1.1.2.r 3-1.1.2 5-1.1.2.1.1 6-1.1.2.1.1.1.r 7-1.1.2.1.1.1 8-1.1.2.1 10-1.1.2.1.2 12-1.1.2.1.2.1.r 13-1.1.2.1.2.1 15-1.1.2.1.1.1.1.r 16-1.1.2.1.1.1.1 19-1.1.2.1.1.1.1.1.1.1.1 20-1.1.2.1.1.1.1.1.1 21-1.1.2.1.1.1.2.3 24-1.1.2.1.1.1.2.1.1.1 28-1.1.2.1.1.1.2.2.1.1 31-1.1 32-1.1 35-1 36-1.1.1.r 37-1.1.1.1.2 38-1.1.1.1.1.1 39-1.1.1 40-1.1.1 43-1.1.3.1 44-1.1.3.1.1
(p3 / perform-01~e.35
:ARG1 (i2 / immunoblot-01~e.31,32
:ARG2~e.36 (c / cell-line~e.39,40
:mod (m2 / medical-condition
:name (n2 / name :op1 "melanoma"~e.38)
:mod (u / uveal~e.37)))
:purpose~e.0,1,2 (a2 / assess-01~e.3
:ARG1 (a3 / and~e.8
:op1 (l / level~e.5
:degree-of~e.6 (e / express-03~e.7
:ARG2~e.15 (m / member~e.16
:ARG1-of (i / include-91
:ARG2 (p2 / pathway~e.20
:name (n3 / name :op1 "MAPK"~e.19))))
:location (r / relative-position
:op1 (g / gene
:name (n4 / name :op1 "RAS"~e.24))
:op2 (g2 / gene
:name (n5 / name :op1 "BRAF"~e.28))
:direction (d2 / downstream~e.21))))
:op2 (a4 / activate-01~e.10
:ARG0~e.12 (p / phosphorylate-01~e.13)
:ARG1 m
:location r)))
:ARG1-of (d3 / describe-01
:ARG0 (t2 / table~e.43 :mod "2A"~e.44))))
# ::id pmid_1592_8660.88 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The expression levels of the downstream members of RAS and BRAF are presented in Figure 1 @ .
# ::alignments 1-1.1.1 2-1.1 3-1.1.1.1.r 5-1.1.1.1.2 6-1.1.1.1 8-1.1.1.1.1.1.1.1.1 9-1.1.1.1.1.1 10-1.1.1.1.1.1.2.1.1 12-1 15-1.2
(p / present-01~e.12
:ARG1 (l / level~e.2
:degree-of (e / express-03~e.1
:ARG2~e.3 (m / member~e.6
:ARG1-of (i / include-91
:ARG2 (a / and~e.9
:op1 (p2 / protein-family
:name (n / name :op1 "RAS"~e.8))
:op2 (e3 / enzyme
:name (n2 / name :op1 "BRAF"~e.10))))
:mod (d / downstream~e.5))))
:location (f / figure~e.15 :mod 3))
# ::id pmid_1592_8660.89 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In response to the constitutively activating BRAF mutation in Ocm 1 , downstream members of the MAPK pathway show activation ( phosphorylated MEK , ERK and ELK ) .
# ::alignments 1-1.3 2-1.3.1.r 4-1.3.1.2.1 4-1.3.1.2.1.r 5-1.3.1.2 7-1.3.1.1.1.1 9-1.3.1 10-1.3.1.3.r 11-1.3.1.3.1.1 12-1.3.1.3.1.2 14-1.1.2 15-1.1 18-1.1.1.1.1.1 19-1.1.1.1 20-1 21-1.2 23-1.2.1.1.2 24-1.2.1.1.1.1 26-1.2.1.2.1.1 27-1.2.1 28-1.2.1.3.1.1
(s / show-01~e.20
:ARG0 (m / member~e.15
:ARG1-of (i / include-91
:ARG2 (p / pathway~e.19
:name (n / name :op1 "MAPK"~e.18)))
:mod (d / downstream~e.14))
:ARG1 (a / activate-01~e.21
:ARG1 (a2 / and~e.27
:op1 (e / enzyme
:name (n2 / name :op1 "MEK"~e.24)
:ARG3-of (p2 / phosphorylate-01~e.23))
:op2 (e2 / enzyme
:name (n3 / name :op1 "ERK"~e.26)
:ARG3-of p2)
:op3 (e3 / enzyme
:name (n4 / name :op1 "ELK"~e.28)
:ARG3-of p2)))
:ARG2-of (r / respond-01~e.1
:ARG1~e.2 (m2 / mutate-01~e.9
:ARG1 (g / gene
:name (n5 / name :op1 "BRAF"~e.7))
:ARG0-of (a3 / activate-01~e.5
:manner~e.4 (c / constitutive~e.4))
:location~e.10 (c2 / cell-line
:name (n6 / name :op1 "Ocm"~e.11 :op2 1~e.12)))))
# ::id pmid_1592_8660.90 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Levels of expression of the downstream members were not different in the two cell lines derived from the same primary tumour ( 92.1 and 92.2 ) , except for phosphorylated MEK , indicating that there had been little clonal divergence between the cell populations during in vitro culturing .
# ::alignments 0-1.2 1-1.2.1.r 2-1.2.1 3-1.2.1.1.r 5-1.2.1.1.1 6-1.2.1.1 8-1.1 8-1.1.r 9-1 9-1.1 9-1.1.r 10-1.4.1.5.1 13-1.3.1 14-1.3.1 14-1.3.2 15-1.3.1.2 16-1.3.1.2.1.r 18-1.3.1.2.1.1 19-1.3.1.2.1.2 20-1.3.1.2.1 22-1.3.1.1.1 23-1.3 24-1.3.2.1.1 27-1.2.1.1.2 28-1.2.1.1.2.1.r 29-1.2.1.1.2.1.2 30-1.2.1.1.2.1.1.1 32-1.4 34-1.4.1.3 37-1.4.1.2 38-1.4.1.4 39-1.4.1 42-1.4.1.1.1 43-1.4.1.1 44-1.4.1.5.r 46-1.4.1.5.1 47-1.4.1.5.1 49-1.4.1.5
(d / differ-02~e.9 :polarity~e.8,9 -~e.8,9
:ARG1 (l / level~e.0
:degree-of~e.1 (e / express-03~e.2
:ARG2~e.3 (m / member~e.6
:mod (d2 / downstream~e.5)
:ARG2-of (e2 / except-01~e.27
:ARG1~e.28 (e3 / enzyme
:name (n / name :op1 "MEK"~e.30)
:ARG3-of (p2 / phosphorylate-01~e.29))))))
:location (a / and~e.23
:op1 (c6 / cell-line~e.13,14
:name (n4 / name :op1 92.1~e.22)
:ARG1-of (d3 / derive-01~e.15
:ARG2~e.16 (t / tumor~e.20
:ARG1-of (s / same-01~e.18)
:mod (p / primary~e.19))))
:op2 (c / cell-line~e.14
:name (n2 / name :op1 92.2~e.24)
:ARG1-of d3))
:ARG0-of (i / indicate-01~e.32
:ARG1 (d4 / diverge-01~e.39
:ARG0 (p3 / population~e.43
:mod (c3 / cell~e.42))
:degree (l2 / little~e.37)
:location (t2 / there~e.34)
:mod (c2 / clone-01~e.38)
:time~e.44 (c4 / culture-01~e.49
:manner (i2 / in-vitro~e.10,46,47)))))
# ::id pmid_1592_8660.91 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Interestingly , compared to the phosphorylation status of these members in Ocm 1 , most cell lines show activation of MEK , ERK and ELK ; however , these cell lines show this activation in the absence of mutations in the upstream RAS and BRAF genes .
# ::alignments 0-1.3 2-1.2.2.r 5-1.2.2.1 6-1.2.2 7-1.2.2.2.r 8-1.2.2.2.1 9-1.2.2.2 10-1.2.2.3.r 11-1.2.2.3.1.1 12-1.2.2.3.1.2 14-1.1.1 15-1.1 16-1.1 17-1 17-1.4 18-1.4.2 19-1.4.2 20-1.4.2 21-1.4.2 22-1.4.2 23-1.4.2 24-1.4.2 26-1.4.r 28-1.4.2 29-1.4.1 30-1.4.1 31-1.4 32-1.4.2 33-1.4.2 34-1.4.3.r 36-1.4.3 37-1.4.3.1.r 38-1.4.3.1 39-1.4.3.1.1.r 41-1.4.3.1.1.1.2 43-1.4.3.1.1.1.1.1 45-1.4.3.1.1 47-1.4.3.1.1.2.1.1 49-1.4.3.1.1.1 49-1.4.3.1.1.2
(s / show-01~e.17
:ARG0 (c / cell-line~e.15,16
:quant (m / most~e.14))
:ARG1 (a / activate-01
:ARG1 (a2 / and
:op1 (e / enzyme
:name (n / name :op1 "MEK"))
:op2 (e2 / enzyme
:name (n2 / name :op1 "ERK"))
:op3 (e3 / enzyme
:name (n3 / name :op1 "ELK")))
:compared-to~e.2 (s2 / status~e.6
:mod (p / phosphorylate-01~e.5)
:poss~e.7 (m2 / member~e.9
:mod (t / this~e.8))
:location~e.10 (c2 / cell-line
:name (n4 / name :op1 "Ocm"~e.11 :op2 1~e.12))))
:mod (i / interesting~e.0)
:concession-of~e.26 (s3 / show-01~e.17,31
:ARG0 c~e.29,30
:ARG1 a~e.18,19,20,21,22,23,24,28,32,33
:condition~e.34 (a3 / absent-01~e.36
:ARG1~e.37 (m3 / mutate-01~e.38
:ARG1~e.39 (a4 / and~e.45
:op1 (g / gene~e.49
:name (n5 / name :op1 "RAS"~e.43)
:location (u / upstream~e.41))
:op2 (g2 / gene~e.49
:name (n6 / name :op1 "BRAF"~e.47)
:location u))))))
# ::id pmid_1592_8660.92 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The levels of total ERK were remarkably similar across all cell lines , with the exception of two cell lines Mel 285 and Mel 290 , which had significantly higher levels of total ERK than the others .
# ::alignments 1-1.1 2-1.1.1.r 3-1.1.1.2 4-1.1.1.1.1 6-1.2 7-1 8-1.3 9-1.3.1.1 10-1.3.1 11-1.3.1 15-1.3.1.2 18-1.3.1 19-1.3.1.2.1.1.2.1.1.3 20-1.3.1.2.1.1.1.1 21-1.3.1.2.1.1.1.2 22-1.3.1.2.1 23-1.3.1.2.1.2.1.1 24-1.3.1.2.1.2.1.2 27-1.3.1.2.1.2.2 28-1.3.1.2.1.2.2 29-1.3.1.2.1.2.2 30-1.3.1.2.1.2.2 32-1.1.1.2 33-1.1.1.1.1 34-1.3.1.2.1.1.2.1.1.3.r 36-1.3.1.2.1.1.2.1.1.3.1
(r2 / resemble-01~e.7
:ARG1 (l / level~e.1
:quant-of~e.2 (e / enzyme
:name (n / name :op1 "ERK"~e.4,33)
:mod (t / total~e.3,32)))
:ARG1-of (r / remarkable-02~e.6)
:location (a / across~e.8
:op1 (c / cell-line~e.10,11,18
:mod (a2 / all~e.9)
:ARG2-of (e2 / except-01~e.15
:ARG1 (a3 / and~e.22
:op1 (c3 / cell-line
:name (n3 / name :op1 "Mel"~e.20 :op2 285~e.21)
:ARG0-of (h / have-03
:ARG1 (l2 / level
:ARG1-of (h2 / high-02
:degree (m / more)
:ARG1-of (s / significant-02)
:compared-to~e.34 (c2 / cell-line~e.19
:mod (o / other~e.36)))
:quant-of e)))
:op2 (c4 / cell-line
:name (n5 / name :op1 "Mel"~e.23 :op2 290~e.24)
:ARG0-of h~e.27,28,29,30))))))
# ::id pmid_1592_8660.93 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In keeping with this observation , these two cell lines also have the highest levels of phosphorylated @-@ ERK .
# ::alignments 1-1.4 2-1.4.1.r 3-1.4.1.1 4-1.4.1 6-1.1.2 7-1.1.1 8-1.1 9-1.1 10-1.3 11-1 13-1.2.1 13-1.2.1.1 13-1.2.1.1.r 14-1.2 15-1.2.2.r 16-1.2.2.2 18-1.2.2.1.1
(h / have-03~e.11
:ARG0 (c / cell-line~e.8,9 :quant 2~e.7
:mod (t / this~e.6))
:ARG1 (l / level~e.14
:ARG1-of (h2 / high-02~e.13
:degree~e.13 (m / most~e.13))
:quant-of~e.15 (e / enzyme
:name (n / name :op1 "ERK"~e.18)
:ARG3-of (p / phosphorylate-01~e.16)))
:mod (a / also~e.10)
:ARG1-of (k / keep-06~e.1
:ARG2~e.2 (o / observe-01~e.4
:ARG1 (t2 / this~e.3))))
# ::id pmid_1592_8660.94 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Figure 2 shows that there is no significant influence of serum on the activity of ERK1 @/@ 2 in these cell lines , as reported recently by Calipel et al ( 2003 ) @ .
# ::alignments 1-1.1 2-1.1.1 4-1 8-1.2.3.1 8-1.2.3.1.r 9-1.2.3 10-1.2 11-1.2.1.r 12-1.2.1 13-1.2.2.r 15-1.2.2 16-1.2.2.1.r 17-1.2.2.1.1.1 19-1.2.2.1.1.1 20-1.2.4.r 21-1.2.4.1 22-1.2.4 23-1.2.4 25-1.3.r 25-1.4.1.1.r 26-1.3 30-1.3.1.1.1.1.1 32-1.3.1.1 33-1.3.1.1.2.1 36-1.4.1.1.1
(s / show-01~e.4
:ARG0 (f / figure~e.1 :mod 2~e.2)
:ARG1 (i / influence-01~e.10
:ARG0~e.11 (s3 / serum~e.12)
:ARG1~e.13 (a / activity-06~e.15
:ARG0~e.16 (e / enzyme
:name (n / name :op1 "ERK1/2"~e.17,19)))
:ARG1-of (s2 / significant-02~e.9 :polarity~e.8 -~e.8)
:location~e.20 (c / cell-line~e.22,23
:mod (t / this~e.21)))
:ARG1-of~e.25 (r / report-01~e.26
:ARG0 (p4 / publication-91
:ARG0 (a2 / and~e.32
:op1 (p / person
:name (n2 / name :op1 "Calipel"~e.30))
:op2 (p2 / person
:mod (o / other~e.33)))))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication-91
:time~e.25 (d2 / date-entity :year 2003~e.36))))
# ::id pmid_1592_8660.95 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Immunohistochemistry
# ::alignments 1-1
(i / immunohistochemistry~e.1)
# ::id pmid_1592_8660.96 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Immunofluorescence results of total and phospho @-@ ERK1 @/@ 2 on a panel of 19 fresh frozen uveal melanoma sections are listed in Table 2 ( B ) @ .
# ::alignments 0-1.1.3 1-1.1 2-1.1.1.r 3-1.1.1.1.2 4-1.1.1 5-1.1.1.2.2 7-1.1.1.1.1.1 7-1.1.1.2.1.1 9-1.2.1 10-1.1.2.r 12-1.1.2 13-1.1.2.1.r 14-1.1.2.1.2.1 15-1.1.2.1.2.2 16-1.1.2.1.2.3 17-1.1.2.1.2 18-1.1.2.1.1.1.1 19-1.1.2.1 21-1 24-1.2 25-1.2.1 27-1.2.2.1.1
(l / list-01~e.21
:ARG1 (r / result-01~e.1
:ARG2~e.2 (a / and~e.4
:op1 (e / enzyme
:name (n / name :op1 "ERK1/2"~e.7)
:mod (t / total~e.3))
:op2 (e2 / enzyme
:name (n3 / name :op1 "ERK1/2"~e.7)
:ARG3-of (p / phosphorylate-01~e.5)))
:location~e.10 (p2 / panel~e.12
:consist-of~e.13 (s / section-01~e.19
:mod (m / medical-condition
:name (n2 / name :op1 "melanoma"~e.18))
:mod (u / uveal~e.17 :quant 19~e.14
:ARG1-of (f / fresh-04~e.15)
:ARG1-of (f2 / freeze-01~e.16))))
:instrument (i / immunofluoresce-01~e.0))
:ARG2 (t2 / table~e.24 :mod 2~e.9,25
:ARG1-of (d2 / describe-01
:ARG0 (f3 / figure :mod "B"~e.27))))
# ::id pmid_1592_8660.97 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In seven of the 19 primary tumours , less than 5 % of the tumour cells stained positively for ERK1 @/@ 2 and nine tumours for phosphorylated ERK1 @/@ 2 .
# ::alignments 1-1.1.3.1 4-1.1.3.2.1.1 5-1.1.3.2.1.2 6-1.1.3.2.1 8-1.1.1.1.2 9-1.1.1.1.2 10-1.1.1.1.2.1.1 11-1.1.1.1.2.1 14-1.1.1.1.1.1 14-1.1.3 15-1.1.1 15-1.1.1.1.1 16-1.1 16-1.2 17-1.1.2 17-1.1.2.r 18-1.1.4.r 19-1.1.4.1.1 21-1.1.4.1.1 22-1 23-1.2.1.1 24-1.2.1 25-1.2.2.r 26-1.2.2.2 27-1.1.4.1.1 27-1.2.2.1.1 29-1.1.4.1.1 29-1.2.2.1.1
(a / and~e.22
:op1 (s / stain-01~e.16
:ARG1 (c / cell~e.15
:ARG1-of (i / include-91
:ARG2 (c2 / cell~e.15
:mod (t / tumor~e.14))
:ARG3 (l / less-than~e.8,9
:op1 (p / percentage-entity~e.11 :value 5~e.10)))
:mod t)
:manner~e.17 (p2 / positive~e.17)
:location (t3 / tumor~e.14 :quant 7~e.1
:ARG1-of (i3 / include-91
:ARG2 (t4 / tumor~e.6 :quant 19~e.4
:mod (p4 / primary~e.5))))
:beneficiary~e.18 (e / enzyme
:name (n2 / name :op1 "ERK1/2"~e.19,21,27,29)))
:op2 (s2 / stain-01~e.16
:ARG1 (t2 / tumor~e.24 :quant 9~e.23
:ARG1-of (i2 / include-91
:ARG2 t4))
:beneficiary~e.25 (e2 / enzyme
:name (n3 / name :op1 "ERK1/2"~e.27,29)
:ARG3-of (p3 / phosphorylate-01~e.26))))
# ::id pmid_1592_8660.98 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Despite the lack of mutations in the RAS and BRAF genes in this set of uveal melanomas , it is noteworthy that we observed phosphorylated ( active ) ERK1 @/@ 2 expression in 10 of 19 tumours .
# ::alignments 0-1.1.4.r 2-1.1.4 3-1.1.4.1.r 4-1.1.4.1 8-1.1.4.1.1.1.1.1 10-1.1.4.1.1 12-1.1.4.1.1.2.1.1 14-1.1.4.1.1.1 14-1.1.4.1.1.2 15-1.1.4.1.1.1.2.r 16-1.1.4.1.1.1.2.1 17-1.1.4.1.1.1.2 18-1.1.4.1.1.1.2.2.r 19-1.1.4.1.1.1.2.2.2 20-1.1.4.1.1.1.2.2.1.1 26-1.1.1 27-1.1 28-1.1.2.1.2 30-1.1.2.1.2.1.1 32-1.1.2.1.1.1 34-1.1.2.1.1.1 35-1.1.2 36-1.1.3.r 37-1.1.3.1 39-1.1.3.2.1.1 40-1.1.3 40-1.1.3.2.1
(n / note-01
:ARG1 (o / observe-01~e.27
:ARG0 (w / we~e.26)
:ARG1 (e / express-01~e.35
:ARG2 (e2 / enzyme
:name (n2 / name :op1 "ERK1/2"~e.32,34)
:ARG3-of (p / phosphorylate-01~e.28
:ARG1-of (m / mean-01
:ARG2 (a / activity-06~e.30)))))
:location~e.36 (t / tumor~e.40 :quant 10~e.37
:ARG1-of (i / include-91
:ARG2 (t2 / tumor~e.40 :quant 19~e.39)))
:concession~e.0 (l / lack-01~e.2
:ARG1~e.3 (m2 / mutate-01~e.4
:ARG1 (a2 / and~e.10
:op1 (g / gene~e.14
:name (n3 / name :op1 "RAS"~e.8)
:location~e.15 (s / set~e.17
:mod (t3 / this~e.16)
:consist-of~e.18 (m3 / medical-condition
:name (n5 / name :op1 "melanoma"~e.20)
:mod (u / uveal~e.19))))
:op2 (g2 / gene~e.14
:name (n4 / name :op1 "BRAF"~e.12)
:location s)))))
:ARG1-of (r / recommend-01))
# ::id pmid_1592_8660.99 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok There was no significant association between ERK1 @/@ 2 activation and tumour location or cell type .
# ::alignments 2-1.3.1 2-1.3.1.r 3-1.3 4-1 6-1.1.1.1.1 8-1.1.1.1.1 9-1.1 11-1.2.1.1 12-1.2.1 12-1.2.1.1.r 13-1.2 14-1.2.2.1 15-1.2.2
(a / associate-01~e.4
:ARG1 (a2 / activate-01~e.9
:ARG1 (e / enzyme
:name (n / name :op1 "ERK1/2"~e.6,8)))
:ARG2 (o / or~e.13
:op1 (l / location~e.12
:location-of~e.12 (t / tumor~e.11))
:op2 (t2 / type-03~e.15
:ARG1 (c / cell~e.14)))
:ARG1-of (s / significant-02~e.3 :polarity~e.2 -~e.2))
# ::id pmid_1592_8660.100 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The scoring system for each antibody cannot be compared between antibodies since the antibodies recognise different epitopes and with different affinities ; therefore , the staining intensity on Western or by immunohistochemistry is relative only to the other samples for the particular antibody used .
# ::alignments 1-1.2.1.1 1-1.2.2.1 2-1.2.1 2-1.2.2 3-1.2.1.1.1.r 4-1.2.1.1.1.1 5-1.2.1.1.1 5-1.2.2.1.1 6-1 6-1.1 6-1.1.r 8-1.2 10-1.2.1.1.1 11-1.2.3 13-1.2.3.1.1 14-1.2.3.1 15-1.2.3.1.2.1 18-1.2.1.1.r 18-1.2.2.1.r 19-1.2.3.1.2.2.1.1 20-1.2.3.1.2.2.1 22-1.2.3 25-1.2.4.1.1.1 26-1.2.4.1.1 29-1.2.4.1.1.2 30-1.2.4.1.1.2.r 31-1.2.4.1.1.2.2 33-1.2.4.1 34-1.2.4.1.3 35-1.2.4.1.2.r 37-1.2.4.1.2.1 38-1.2.4.1.2 38-1.2.4.1.2.3 38-1.2.4.1.2.3.r 39-1.2.4.1.2.2.r 41-1.2.4.1.2.2.1 42-1.2.4.1.2.2 43-1.2.4.1.2.2.2
(p2 / possible-01~e.6 :polarity~e.6 -~e.6
:ARG1 (c / compare-01~e.8
:ARG1 (s / system~e.2
:instrument-of~e.18 (s2 / score-01~e.1
:ARG1~e.3 (a / antibody~e.5,10
:mod (e / each~e.4))))
:ARG2 (s3 / system~e.2
:instrument-of~e.18 (s4 / score-01~e.1
:ARG1 (a2 / antibody~e.5)))
:ARG1-of (c2 / cause-01~e.11,22
:ARG0 (r / recognize-02~e.14
:ARG0 a~e.13
:ARG1 (e2 / epitope
:ARG1-of (d / differ-02~e.15)
:ARG0-of (h / have-03
:ARG1 (a3 / affinity~e.20
:ARG1-of d~e.19)))))
:ARG0-of (c3 / cause-01
:ARG1 (r2 / relative-05~e.33
:ARG1 (i / intensity~e.26
:mod (s5 / stain-01~e.25)
:instrument~e.30 (o / or~e.29
:op1 (i3 / immunoblot-01)
:op2 (i2 / immunohistochemistry~e.31)))
:ARG3~e.35 (t / thing~e.38
:mod (o3 / other~e.37)
:beneficiary~e.39 (a4 / antibody~e.42
:mod (p / particular~e.41)
:ARG1-of (u / use-01~e.43))
:ARG1-of~e.38 (s6 / sample-01~e.38))
:mod (o2 / only~e.34)))))
# ::id pmid_1684_6534.1 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok MUC1 alters oncogenic events and transcription in human breast cancer cells ( PMID : 16846534 )
# ::alignments 0-1.1.1.1 1-1 2-1.2.1.1 2-1.2.1.1.1.2.1 3-1.2.1 4-1.2 5-1.2.2 6-1.3.r 7-1.3.2 8-1.3.1.2.1 9-1.3.1.2.2 10-1.3
(a / alter-01~e.1
:ARG0 (p / protein
:name (n / name :op1 "MUC1"~e.0))
:ARG1 (a2 / and~e.4
:op1 (e / event~e.3
:ARG0-of (c / cause-01~e.2
:ARG1 (d3 / disease :wiki "Cancer"
:name (n3 / name :op1 "cancer"~e.2))))
:op2 (t / transcribe-01~e.5))
:location~e.6 (c3 / cell~e.10
:source (d2 / disease :wiki "Breast_cancer"
:name (n2 / name :op1 "breast"~e.8 :op2 "cancer"~e.9))
:mod (h / human~e.7))
:ARG1-of (d / describe-01
:ARG0 (p2 / publication-91 :ARG8 "PMID16846534")))
# ::id pmid_1684_6534.8 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Results
# ::alignments 1-1 1-1.1 1-1.1.r
(t / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1))
# ::id pmid_1684_6534.9 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Transcription of several genes was altered after transfection of MUC1 siRNA , including decreased MAP2K1 @ ( MEK1 ) , JUN , PDGFA , CDC25A , VEGF @ and ITGAV @ ( integrin α @ v ) , and increased TNF , RAF1 , and MMP2 @ .
# ::alignments 0-1.1 0-1.1.2.1.1.1 0-1.1.2.1.1.2 0-1.1.2.1.1.3 0-1.1.2.1.1.4 0-1.1.2.1.1.5 0-1.1.2.1.1.6 0-1.1.2.1.2.1 0-1.1.2.1.2.2 0-1.1.2.1.2.3 2-1.1.1.1 3-1.1.1 3-1.1.2.1.1.1.1.2.1 5-1 6-1.2 7-1.2.1 8-1.2.1.1.r 9-1.2.1.1.2.1.1.1 10-1.2.1.1.1.1 12-1.1.2 13-1.1.2.1.1.7 15-1.1.2.1.1.1.1.1.1 18-1.1.2.1.1.1.1.2.1.1.1.1.1 22-1.1.2.1.1.2.1.1.1 26-1.1.2.1.1.3.1.1.1 30-1.1.2.1.1.4.1.1.1 34-1.1.2.1.1.5.1.1.1 36-1.1.2.1.1 38-1.1.2.1.1.6.1.1.1 41-1.1.2.1.1.6.1.2.1.1.1 48-1.1.2.1.2 49-1.1.2.1.2.4 51-1.1.2.1.2.1.1.1.1 55-1.1.2.1.2.2.1.1.1 60-1.1.2.1.2.3.1.1.1
(a / alter-01~e.5
:ARG1 (t / transcribe-01~e.0
:ARG1 (g / gene~e.3
:quant (s / several~e.2))
:ARG2-of (i / include-01~e.12
:ARG1 (a3 / and
:op1 (a4 / and~e.36
:op1 (t3 / transcribe-01~e.0
:ARG1 (g2 / gene
:name (n3 / name :op1 "MAP2K1"~e.15)
:ARG1-of (m / mean-01
:ARG2 (g8 / gene~e.3
:ARG0-of (e / encode-01
:ARG1 (e2 / enzyme
:name (n13 / name :op1 "MEK1"~e.18)))))))
:op2 (t4 / transcribe-01~e.0
:ARG1 (g3 / gene
:name (n4 / name :op1 "JUN"~e.22)))
:op3 (t5 / transcribe-01~e.0
:ARG1 (g4 / gene
:name (n5 / name :op1 "PDGFA"~e.26)))
:op4 (t6 / transcribe-01~e.0
:ARG1 (g5 / gene
:name (n6 / name :op1 "CDC25A"~e.30)))
:op5 (t7 / transcribe-01~e.0
:ARG1 (g6 / gene
:name (n7 / name :op1 "VEGF"~e.34)))
:op6 (t8 / transcribe-01~e.0
:ARG1 (g7 / gene
:name (n8 / name :op1 "ITGAV"~e.38)
:ARG0-of (e3 / encode-01
:ARG1 (p2 / protein
:name (n9 / name :op1 "integrin"~e.41 :op2 "αv")))))
:ARG1-of (d / decrease-01~e.13))
:op2 (a5 / and~e.48
:op1 (t9 / transcribe-01~e.0
:ARG1 (g9 / gene
:name (n10 / name :op1 "TNF"~e.51)))
:op2 (t10 / transcribe-01~e.0
:ARG1 (g10 / gene
:name (n11 / name :op1 "RAF1"~e.55)))
:op3 (t11 / transcribe-01~e.0
:ARG1 (g11 / gene
:name (n12 / name :op1 "MMP2"~e.60)))
:ARG1-of (i2 / increase-01~e.49)))))
:time (a2 / after~e.6
:op1 (t2 / transfect-01~e.7
:ARG2~e.8 (n14 / nucleic-acid
:name (n / name :op1 "siRNA"~e.10)
:ARG0-of (e4 / encode-01
:ARG1 (p / protein
:name (n2 / name :op1 "MUC1"~e.9)))))))
# ::id pmid_1684_6534.10 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Additional changes were seen at the protein level , such as increased expression of c @-@ Myc , heightened phosphorylation of AKT , and decreased activation of MEK1 @/@ 2 and ERK1 @/@ 2 .
# ::alignments 0-1.1.2 1-1.1 3-1 4-1.1.1.r 6-1.1.1.1 7-1.1.1 9-1.1.3.r 10-1.1.3.r 11-1.1.3.1.2 12-1.1.3.1 13-1.1.3.1.1.r 14-1.1.3.1.1.1.1 16-1.1.3.1.1.1.1 18-1.1.3.2.2 19-1.1.3.2 20-1.1.3.2.1.r 21-1.1.3.2.1.1.1 23-1.1.3 24-1.1.3.3.2 25-1.1.3.3 26-1.1.3.3.1.r 27-1.1.3.3.1.1.1.1 31-1.1.3.3.1.3.1.1
(s / see-01~e.3
:ARG1 (c / change-01~e.1
:ARG1~e.4 (l / level~e.7
:quant-of (p / protein~e.6))
:mod (a / additional~e.0)
:example~e.9,10 (a2 / and~e.23
:op1 (e / express-03~e.12
:ARG2~e.13 (p3 / protein
:name (n / name :op1 "c-Myc"~e.14,16))
:ARG1-of (i / increase-01~e.11))
:op2 (p2 / phosphorylate-01~e.19
:ARG1~e.20 (e2 / enzyme
:name (n2 / name :op1 "AKT"~e.21))
:ARG1-of (h / heighten-01~e.18))
:op3 (a3 / activate-01~e.25
:ARG1~e.26 (a4 / and
:op1 (e3 / enzyme
:name (n3 / name :op1 "MEK1"~e.27))
:op2 (e4 / enzyme
:name (n4 / name :op1 "MEK2"))
:op3 (e5 / enzyme
:name (n5 / name :op1 "ERK1"~e.31))
:op4 (e6 / enzyme
:name (n6 / name :op1 "ERK2")))
:ARG1-of (d / decrease-01~e.24)))))
# ::id pmid_1684_6534.11 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok These were correlated with cellular events , as MUC1 siRNA in the MDA @-@ MB @-@ 468 line decreased proliferation and invasion , and increased stress @-@ induced apoptosis .
# ::alignments 0-1.1 2-1 3-1.2.r 4-1.2.1 5-1.2 8-1.3.1.1.1.2.1.1.1 9-1.3.1.1.1.1.1 12-1.3.1.3.1.1 14-1.3.1.3.1.1 16-1.3.1.3.1.1 17-1.3.1.3 18-1.3.1.1 19-1.3.1.1.2.1 20-1.3.1.1.2 21-1.3.1.1.2.2 23-1.3.1 24-1.3.1.2 25-1.3.1.2.2.1.1 27-1.3.1.2.2.1 28-1.3.1.2.2
(c / correlate-01~e.2
:ARG1 (t / this~e.0)
:ARG2~e.3 (e / event~e.5
:mod (c2 / cell~e.4))
:ARG1-of (c4 / cause-01
:ARG0 (a / and~e.23
:op1 (d / decrease-01~e.18
:ARG0 (n4 / nucleic-acid
:name (n / name :op1 "siRNA"~e.9)
:ARG0-of (e2 / encode-01
:ARG1 (p / protein
:name (n2 / name :op1 "MUC1"~e.8))))
:ARG1 (a3 / and~e.20
:op1 (p2 / proliferate-01~e.19)
:op2 (i / invade-01~e.21)))
:op2 (i2 / increase-01~e.24
:ARG0 n4
:ARG1 (a2 / apoptosis~e.28
:ARG2-of (i3 / induce-01~e.27
:ARG0 (s / stress~e.25))))
:location (c3 / cell-line~e.17
:name (n3 / name :op1 "MDA-MB-468"~e.12,14,16)))))
# ::id pmid_1684_6534.12 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Intriguingly , BT @-@ 20 cells displayed similar levels of apoptosis regardless of siRNA , and actually increased proliferation after MUC1 siRNA .
# ::alignments 0-1.3 2-1.1.1.1.1 4-1.1.1.1.1 5-1.1.1 6-1.1 7-1.1.2.2 8-1.1.2 9-1.1.2.1.r 10-1.1.2.1 11-1.1.3 13-1.1.3.1.1.1 15-1 16-1.2.3 17-1.2 18-1.2.2 19-1.2.4 20-1.2.4.1.2.1.1.1 21-1.1.3.1.1.1 21-1.2.4.1.1.1
(a5 / and~e.15
:op1 (d / display-01~e.6
:ARG0 (c / cell-line~e.5
:name (n / name :op1 "BT-20"~e.2,4))
:ARG1 (l / level~e.8
:degree-of~e.9 (a2 / apoptosis~e.10)
:ARG1-of (r / resemble-01~e.7))
:ARG1-of (r2 / regardless-91~e.11
:ARG2 (n5 / nucleic-acid
:name (n2 / name :op1 "siRNA"~e.13,21))))
:op2 (i / increase-01~e.17
:ARG0 c
:ARG1 (p / proliferate-01~e.18
:ARG0 c)
:ARG1-of (a / actual-02~e.16)
:time (a4 / after~e.19
:op1 (n6 / nucleic-acid
:name (n3 / name :op1 "siRNA"~e.21)
:ARG0-of (e / encode-01
:ARG1 (p2 / protein
:name (n4 / name :op1 "MUC1"~e.20))))))
:ARG0-of (i2 / intrigue-01~e.0))
# ::id pmid_1684_6534.100 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Results
# ::alignments 1-1 1-1.1 1-1.1.r
(t / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1))
# ::id pmid_1684_6534.101 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok siRNA transfection decreases MUC1 expression in breast cancer cell lines
# ::alignments 1-1.1.1.1.1 2-1.1 3-1 4-1.2.1.1.1 5-1.2 6-1.2.2.r 7-1.2.2.1.2.1 8-1.2.2.1.2.2 9-1.2.2 10-1.2.2
(d / decrease-01~e.3
:ARG0 (t / transfect-01~e.2
:ARG2 (n3 / nucleic-acid
:name (n / name :op1 "siRNA"~e.1)))
:ARG1 (e / express-03~e.5
:ARG2 (p / protein
:name (n2 / name :op1 "MUC1"~e.4))
:ARG3~e.6 (c / cell-line~e.9,10
:source (d2 / disease :wiki "Breast_cancer"
:name (n4 / name :op1 "breast"~e.7 :op2 "cancer"~e.8)))))
# ::id pmid_1684_6534.102 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Two human breast cancer cell lines , MDA @-@ MB @-@ 468 and BT @-@ 20 , were transiently transfected with a pool of four siRNA oligonucleotides directed against the MUC1 mRNA ( 468.siMUC1 and BT.siMUC1 ) , or a control oligonucleotide directed against luciferase ( 468.siLuc and BT.siLuc ) .
# ::alignments 0-1.1.1 1-1.1.3.3 2-1.1.3.2.1 3-1.1.3.2.2 4-1.1 5-1.1 7-1.1.2.1.1.1.1 9-1.1.2.1.1.1.1 11-1.1.2.1.1.1.1 12-1.1.2.1 13-1.1.2.1.2.1.1 15-1.1.2.1.2.1.1 18-1.3 19-1 20-1.2.r 22-1.2.1 23-1.2.1.1.r 24-1.2.1.1.1 25-1.2.1.1.2.1.1 26-1.2.1.1 27-1.2.1.2 30-1.2.1.2.1.2.1.1.1 31-1.2.1.2.1.1.1 33-1.2.1.3.1.1.1.1 35-1.2.1.3.1.2.1.1 38-1.2 40-1.2.2.1 41-1.2.2 42-1.2.2.2 44-1.2.2.2.1 46-1.2.2.3.1.1.1.1 48-1.2.2.3.1.2.1.1
(t / transfect-01~e.19
:ARG1 (c / cell-line~e.4,5 :quant 2~e.0
:ARG1-of (m / mean-01
:ARG2 (a / and~e.12
:op1 (c3 / cell-line
:name (n / name :op1 "MDA-MB-468"~e.7,9,11))
:op2 (c4 / cell-line
:name (n2 / name :op1 "BT-20"~e.13,15))))
:source (d3 / disease :wiki "Breast_cancer"
:name (n8 / name :op1 "breast"~e.2 :op2 "cancer"~e.3)
:mod (h / human~e.1)))
:ARG2~e.20 (o / or~e.38
:op1 (p / pool~e.22
:consist-of~e.23 (o2 / oligonucleotide~e.26 :quant 4~e.24
:mod (n11 / nucleic-acid
:name (n3 / name :op1 "siRNA"~e.25)))
:ARG1-of (d / direct-01~e.27
:ARG2 (n12 / nucleic-acid
:name (n4 / name :op1 "mRNA"~e.31)
:ARG0-of (e2 / encode-01
:ARG1 (p2 / protein
:name (n5 / name :op1 "MUC1"~e.30)))))
:ARG1-of (m2 / mean-01
:ARG2 (a2 / and
:op1 (c6 / cell-line
:name (n6 / name :op1 "468.siMUC1"~e.33))
:op2 (c7 / cell-line
:name (n7 / name :op1 "BT.siMUC1"~e.35)))))
:op2 (o5 / oligonucleotide~e.41
:mod (c5 / control~e.40)
:ARG1-of (d2 / direct-01~e.42
:ARG2 (l / luciferase~e.44))
:ARG1-of (m3 / mean-01
:ARG2 (a3 / and
:op1 (c8 / cell-line
:name (n9 / name :op1 "468.siLuc"~e.46))
:op2 (c9 / cell-line
:name (n10 / name :op1 "BT.siLuc"~e.48))))))
:manner (t2 / transient-02~e.18))
# ::id pmid_1684_6534.103 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Both cell lines express high levels of MUC1 , making them promising targets for this analysis .
# ::alignments 0-1.2 1-1.2 2-1.2 3-1 4-1.1.1 5-1.1 6-1.1.2.r 7-1.1.2.1.1 9-1.3 9-1.3.1.3 11-1.3.1.3 12-1.3.1 12-1.3.1.2 12-1.3.1.2.r 13-1.3.1.2.1.r 14-1.3.1.2.1.1 15-1.3.1.2.1
(e / express-03~e.3
:ARG2 (l / level~e.5
:ARG1-of (h / high-02~e.4)
:quant-of~e.6 (p / protein
:name (n / name :op1 "MUC1"~e.7)))
:ARG3 c2~e.0,1,2
:ARG0-of (m / make-02~e.9
:ARG1 (c2 / cell-line~e.12
:mod (b / both)
:ARG1-of~e.12 (t / target-01~e.12
:ARG0~e.13 (a / analyze-01~e.15
:mod (t2 / this~e.14)))
:ARG0-of (p2 / promise-01~e.9,11))))
# ::id pmid_1684_6534.104 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Western blots ( Figure 1a ) show successful knockdown of both the extracellular domain and cytoplasmic tail fragments of MUC1 ; luciferase siRNA does not substantially change the level of MUC1 compared to parental cells .
# ::alignments 0-1.1.1 1-1.1.1 3-1.1.1.1.1 5-1.1.1.1.1.1 8-1.1 9-1.1.2.2 10-1.1.2 14-1.1.2.1.1.1 16-1.1.2.1 17-1.1.2.1.2.1.1 18-1.1.2.1.2.1 19-1.1.2.1.2 21-1.2.3.1.1.1 23-1.2.2.2.1 24-1.2.2.1.1 26-1.2.1 26-1.2.1.r 27-1.2.4 28-1.2 30-1.2.3 32-1.1.2.1.1.2.1.1 32-1.2.3.1.1.1 33-1.2.5.r 35-1.2.5.1 36-1.2.5
(m / multi-sentence
:snt1 (s / show-01~e.8
:ARG0 (i / immunoblot-01~e.0,1
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.3 :mod "1a"~e.5)))
:ARG1 (k / knock-down-02~e.10
:ARG1 (a / and~e.16
:op1 (p / protein-segment
:mod (e / extracellular~e.14)
:part-of (p2 / protein
:name (n2 / name :op1 "MUC1"~e.32)))
:op2 (f2 / fragment~e.19
:part-of (t2 / tail~e.18
:mod (c / cytoplasm~e.17)
:part-of p2)))
:ARG0-of (s3 / succeed-01~e.9)))
:snt2 (c2 / change-01~e.28 :polarity~e.26 -~e.26
:ARG0 (n4 / nucleic-acid
:name (n3 / name :op1 "siRNA"~e.24)
:ARG0-of (e2 / encode-01
:ARG1 (l2 / luciferase~e.23)))
:ARG1 (l / level~e.30
:quant-of (p3 / protein
:name (n5 / name :op1 "MUC1"~e.21,32)))
:degree (s2 / substantial~e.27)
:compared-to~e.33 (c3 / cell~e.36
:mod (p4 / parental~e.35))))
# ::id pmid_1684_6534.105 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok 468.siMUC1 show a substantial decrease in the amount of MUC1 @-@ CT , while BT.siMUC1 show slightly less knockdown of MUC1 @-@ CT .
# ::alignments 0-1.1.1.1.1 1-1.1 3-1.1.2.2 4-1.1.2 5-1.1.2.1.r 7-1.1.2.1 8-1.1.2.1.1.r 9-1.1.2.1.1.1.1 11-1.1.2.1.1.1.1 13-1 14-1.2.1.1.1 15-1.2 16-1.2.2.2.1 17-1.2.2.2 18-1.2.2 19-1.2.2.1.r 20-1.2.2.1 21-1.2.2.1 22-1.2.2.1
(c / contrast-01~e.13
:ARG1 (s / show-01~e.1
:ARG0 (c2 / cell-line
:name (n2 / name :op1 "468.siMUC1"~e.0))
:ARG1 (d / decrease-01~e.4
:ARG1~e.5 (a / amount~e.7
:quant-of~e.8 (p / protein-segment
:name (n / name :op1 "MUC1-CT"~e.9,11)))
:ARG2 (s2 / substantial~e.3)))
:ARG2 (s3 / show-01~e.15
:ARG0 (c3 / cell-line
:name (n3 / name :op1 "BT.siMUC1"~e.14))
:ARG1 (k / knock-down-02~e.18
:ARG1~e.19 p~e.20,21,22
:ARG2 (l / less~e.17
:degree (s4 / slight~e.16)))))
# ::id pmid_1684_6534.106 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Both MDA @-@ MB @-@ 468 and BT @-@ 20 display a less dramatic decrease of MUC1 extracellular domain compared to MUC1 @-@ CT ( Figure 1a ) ; this likely represents protein synthesized prior to transfection , and may reflect differences in the turnover rates of the two subunits .
# ::alignments 1-1.1.1.1.1 3-1.1.1.1.1 5-1.1.1.1.1 6-1.1 7-1.1.2.1.1 9-1.1.2.1.1 10-1 12-1.2.2.1 13-1.2.2 14-1.2 16-1.2.1.2.1.1 17-1.2.1.1 19-1.2.3.r 21-1.2.3.1.1 23-1.2.3.1.1 25-1.3.1 27-1.3.1.1 32-1.4.2 33-1.4 34-1.2.1 34-1.4.1 35-1.4.1.1 36-1.4.1.1.1 37-1.4.1.1.1.1.r 38-1.4.1.1.1.1 40-1.5.1.1.2 41-1.5.2 42-1.5 43-1.5.1 44-1.5.1.1.r 46-1.5.1.1.1 47-1.5.1.1
(d / display-01~e.10
:ARG0 (a / and~e.6
:op1 (c / cell-line
:name (n / name :op1 "MDA-MB-468"~e.1,3,5))
:op2 (c2 / cell-line
:name (n2 / name :op1 "BT-20"~e.7,9)))
:ARG1 (d2 / decrease-01~e.14
:ARG1 (p2 / protein-segment~e.34
:mod (e / extracellular~e.17)
:part-of (p / protein
:name (n3 / name :op1 "MUC1"~e.16)))
:ARG2 (d3 / dramatic~e.13
:degree (l / less~e.12))
:compared-to~e.19 (p3 / protein-segment
:name (n4 / name :op1 "MUC1-CT"~e.21,23)))
:ARG1-of (d4 / describe-01
:ARG0 (f / figure~e.25 :mod "1a"~e.27))
:ARG0-of (r / represent-01~e.33
:ARG1 (p4 / protein~e.34
:ARG1-of (s / synthesize-01~e.35
:time (p6 / prior~e.36
:op1~e.37 (t / transfect-01~e.38))))
:ARG1-of (l2 / likely-01~e.32))
:ARG1-of (r2 / reflect-01~e.42
:ARG2 (d5 / differ-02~e.43
:ARG1~e.44 (r3 / rate~e.47
:degree-of (t2 / turnover~e.46)
:poss (a2 / and~e.40
:op1 p2
:op2 p3)))
:ARG1-of (p5 / possible-01~e.41)))
# ::id pmid_1684_6534.107 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Analysis of the MUC1 extracellular domain by flow cytometry confirms that both cell lines substantially decrease MUC1 expression after siRNA ( Figure 1b ) .
# ::alignments 0-1.1 1-1.1.1.r 3-1.1.1.2.1.1 4-1.1.1.1 6-1.1.2.r 7-1.1.2.1 8-1.1.2 9-1 10-1.2.r 11-1.2.1.1 12-1.2.1 13-1.2.1 14-1.2.3 15-1.2 16-1.2.2.1 17-1.2.2 18-1.2.4 19-1.2.4.1.1.1 21-1.3.1 23-1.3.1.1
(c / confirm-01~e.9
:ARG0 (a / analyze-01~e.0
:ARG1~e.1 (p / protein-segment
:mod (e / extracellular~e.4)
:part-of (p2 / protein
:name (n / name :op1 "MUC1"~e.3)))
:instrument~e.6 (c2 / cytometry~e.8
:mod (f / flow~e.7)))
:ARG1~e.10 (d / decrease-01~e.15
:ARG0 (c3 / cell-line~e.12,13
:mod (b / both~e.11))
:ARG1 (e2 / express-03~e.17
:ARG2 p2~e.16)
:ARG2 (s / substantial~e.14)
:time (a2 / after~e.18
:op1 (n3 / nucleic-acid
:name (n2 / name :op1 "siRNA"~e.19))))
:ARG1-of (d2 / describe-01
:ARG0 (f2 / figure~e.21 :mod "1b"~e.23)))
# ::id pmid_1684_6534.108 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok By flow cytometry , 468.siMUC1 averaged 75 % knockdown of MUC1 compared to 468.siLuc ; and BT.siMUC1 averaged 50 % knockdown relative to BT.siLuc .
# ::alignments 1-1.3.1 2-1.3 4-1.1.1.1.1 5-1.1 6-1.1.3.1 7-1.1.3 8-1.1.2 9-1.1.2.1.r 10-1.1.2.1.1.1 11-1.1.1.2.r 13-1.1.1.2.1.1 15-1 16-1.2.1.1.1 17-1.2 18-1.2.3.1 19-1.2.3 20-1.2.2 21-1.2.1 21-1.2.1.2 21-1.2.1.2.r 22-1.2.1.2.1.r 23-1.2.1.2.1.1.1
(a / and~e.15
:op1 (a2 / average-01~e.5
:ARG0 (c2 / cell-line
:name (n2 / name :op1 "468.siMUC1"~e.4)
:compared-to~e.11 (c3 / cell-line
:name (n3 / name :op1 "468.siLuc"~e.13)))
:ARG1 (k / knock-down-02~e.8
:ARG1~e.9 (p2 / protein
:name (n / name :op1 "MUC1"~e.10)))
:ARG2 (p / percentage-entity~e.7 :value 75~e.6))
:op2 (a3 / average-01~e.17
:ARG0 (c5 / cell-line~e.21
:name (n5 / name :op1 "BT.siMUC1"~e.16)
:ARG1-of~e.21 (r / relative-05~e.21
:ARG3~e.22 (c4 / cell-line
:name (n4 / name :op1 "BT.siLuc"~e.23))))
:ARG1 (k2 / knock-down-02~e.20)
:ARG2 (p3 / percentage-entity~e.19 :value 50~e.18))
:time (c / cytometry~e.2
:mod (f / flow~e.1)))
# ::id pmid_1684_6534.109 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok These effects could be titrated with the concentration of siRNA , were seen as early as 24 hours post @-@ transfection ( data not shown ) and lasted to at least 96 h post @-@ transfection ( Figure 1b ) .
# ::alignments 0-1.1.1.2.1 1-1.1.1.2 2-1.1 4-1.1.1 5-1.1.1.1.r 7-1.1.1.1 8-1.1.1.1.1.r 9-1.1.1.1.1.1.1 12-1.2 13-1.2.3.r 14-1.2.3.2.3 15-1.2.3.r 16-1.2.3.2.1 17-1.2.3.2.2 18-1.2.3 20-1.2.3.1 22-1.2.2.1 23-1.2.2.1.1.1 23-1.2.2.1.1.1.r 24-1.2.2.1.1 26-1 27-1.3 28-1.3.3.r 29-1.3.3 30-1.3.3 31-1.3.2.1.2.1 32-1.3.2.1.2.2 33-1.2.3 33-1.3.2.1 35-1.2.3.1 37-1.3.4.1 39-1.3.4.1.1
(a / and~e.26
:op1 (p / possible-01~e.2
:ARG1 (t / titrate-01~e.4
:ARG0~e.5 (c / concentrate-02~e.7
:ARG1~e.8 (n2 / nucleic-acid
:name (n / name :op1 "siRNA"~e.9)))
:ARG1 (a2 / affect-01~e.1
:mod (t2 / this~e.0))))
:op2 (s / see-01~e.12
:ARG1 a2
:ARG1-of (d / describe-01
:ARG0 (d2 / data~e.22
:ARG1-of (s2 / show-01~e.24 :polarity~e.23 -~e.23)))
:time~e.13,15 (a3 / after~e.18,33
:op1 (t3 / transfect-01~e.20,35)
:quant (t4 / temporal-quantity :quant 24~e.16
:unit (h / hour~e.17)
:mod (e2 / early~e.14))))
:op3 (l / last-01~e.27
:ARG1 a2
:ARG2 (u / until
:op1 (a4 / after~e.33
:op1 t3
:quant (t5 / temporal-quantity :quant 96~e.31
:unit h~e.32)))
:mod~e.28 (a5 / at-least~e.29,30)
:ARG1-of (d3 / describe-01
:ARG0 (f / figure~e.37 :mod "1b"~e.39))))
# ::id pmid_1684_6534.110 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok All experiments were conducted within 48 to 96 hours after siRNA transfection .
# ::alignments 0-1.1.1 1-1.1 3-1 4-1.2 4-1.2.2 4-1.2.2.1.1.1.r 4-1.2.2.r 5-1.2.2.1.1.1 7-1.2.2.1.2.1 8-1.2.2.1.1.2 9-1.2 10-1.2.1.1.1.1 11-1.2.1
(c / conduct-01~e.3
:ARG1 (e / experiment-01~e.1
:mod (a / all~e.0))
:time (a2 / after~e.4,9
:op1 (t / transfect-01~e.11
:ARG2 (n2 / nucleic-acid
:name (n / name :op1 "siRNA"~e.10)))
:quant~e.4 (u / up-to~e.4
:op1 (v / value-interval
:op1 (t2 / temporal-quantity :quant~e.4 48~e.5
:unit (h / hour~e.8))
:op2 (t3 / temporal-quantity :quant 96~e.7
:unit h)))))
# ::id pmid_1684_6534.111 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Similar results were obtained using two independent oligonucleotides designed in our lab ( data not shown ) , designated ' 882 ' and ' 956 ' for the initial codon recognized by each .
# ::alignments 0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 3-1 4-1.2 5-1.2.1.1 6-1.2.1.2 6-1.2.1.2.1 6-1.2.1.2.1.r 7-1.2.1 7-1.2.1.4.1.1 7-1.2.1.4.1.2 8-1.2.1.5 10-1.2.1.5.1.1 10-1.2.1.5.1.1.r 13-1.2.1.3.1 14-1.2.1.3.1.1.1 14-1.2.1.3.1.1.1.r 15-1.2.1.3.1.1 18-1.2.1.4 20-1.2.1.4.1.1.1 22-1.2.1.4.1 24-1.2.1.4.1.2.1 28-1.2.1.4.2.1.1 29-1.2.1.4.2.1 30-1.2.1.4.2.1.2
(o / obtain-01~e.3
:ARG1 (t / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1)
:ARG1-of (r2 / resemble-01~e.0))
:manner (u / use-01~e.4
:ARG1 (o2 / oligonucleotide~e.7 :quant 2~e.5
:ARG0-of (d / depend-01~e.6 :polarity~e.6 -~e.6)
:ARG1-of (d3 / describe-01
:ARG0 (d4 / data~e.13
:ARG1-of (s / show-01~e.15 :polarity~e.14 -~e.14)))
:ARG1-of (d5 / designate-01~e.18
:ARG2 (a / and~e.22
:op1 (o3 / oligonucleotide~e.7 :mod 882~e.20)
:op2 (o4 / oligonucleotide~e.7 :mod 956~e.24))
:ARG1-of (c / cause-01
:ARG0 (c2 / codon~e.29
:mod (i / initial~e.28)
:ARG1-of (r3 / recognize-02~e.30
:location o2))))
:ARG1-of (d2 / design-01~e.8
:location (l / laboratory
:poss~e.10 (w / we~e.10))))))
# ::id pmid_1684_6534.112 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Transcriptional changes are seen after MUC1 siRNA
# ::alignments 1-1.1.1 2-1.1 4-1 5-1.2 6-1.2.1.2.1.1.1 7-1.2.1.1.1
(s / see-01~e.4
:ARG1 (c / change-01~e.2
:ARG1 (t / transcribe-01~e.1))
:time (a / after~e.5
:op1 (n3 / nucleic-acid
:name (n / name :op1 "siRNA"~e.7)
:ARG0-of (e / encode-01
:ARG1 (p / protein
:name (n2 / name :op1 "MUC1"~e.6))))))
# ::id pmid_1684_6534.113 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Recent work indicates that MUC1 may affect transcription both directly via interaction with transcription factors and indirectly ( for example , through modulating signaling ) .
# ::alignments 0-1.1.1 1-1.1 2-1 3-1.2.r 4-1.2.1.1.1.1 5-1.2 6-1.2.1 7-1.2.1.2 9-1.2.1.3.1 11-1.2.1.3.1.1 12-1.2.1.3.1.1.2.r 13-1.2.1.3.1.1.2.1 14-1.2.1.3.1.1.2 15-1.2.1.3 16-1.2.1.3.1 16-1.2.1.3.2 16-1.2.1.3.2.1 16-1.2.1.3.2.1.r 18-1.2.1.3.2.2.r 19-1.2.1.3.2.2.r 22-1.2.1.3.2.2 23-1.2.1.3.2.2.2
(i / indicate-01~e.2
:ARG0 (w / work-01~e.1
:time (r / recent~e.0))
:ARG1~e.3 (p / possible-01~e.5
:ARG1 (a / affect-01~e.6
:ARG0 (p2 / protein
:name (n / name :op1 "MUC1"~e.4))
:ARG1 (t / transcribe-01~e.7)
:manner (a2 / and~e.15
:op1 (d / direct-02~e.9,16
:manner (i2 / interact-01~e.11
:ARG0 p2
:ARG1~e.12 (f / factor~e.14
:ARG0-of t~e.13)))
:op2 (d2 / direct-02~e.16 :polarity~e.16 -~e.16
:example~e.18,19 (m / modulate-01~e.22
:ARG0 p2
:ARG1 (s / signal-07~e.23)))))))
# ::id pmid_1684_6534.114 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To study the effects of MUC1 knockdown in breast cancer cell lines , real @-@ time PCR arrays were used to analyze transcription of 84 genes implicated in cancer .
# ::alignments 1-1.3 3-1.3.1 4-1.3.1.1.r 5-1.3.1.1.1.1.1 6-1.3.1.1 7-1.3.1.2.r 8-1.3.1.2.1.2.1 9-1.3.1.2.1.2.2 10-1.3.1.2 11-1.3.1.2 13-1.1.1.2 15-1.1.1.2 16-1.1.1 16-1.1.1.1 16-1.1.1.1.r 17-1.1 19-1 19-1.3.r 21-1.2 22-1.2.1 23-1.2.1.1.r 24-1.2.1.1.1 25-1.2.1.1 26-1.2.1.1.2 27-1.2.1.1.2.1.r 28-1.2.1.1.2.1.2.1
(u / use-01~e.19
:ARG1 (a / array-01~e.17
:mod (r2 / react-01~e.16
:ARG0~e.16 (p / polymerase~e.16)
:mod (r / real-time~e.13,15)
:mod (c4 / chain)))
:ARG2 (a2 / analyze-01~e.21
:ARG1 (t / transcribe-01~e.22
:ARG1~e.23 (g / gene~e.25 :quant 84~e.24
:ARG1-of (i / implicate-01~e.26
:ARG2~e.27 (d / disease :wiki "Cancer"
:name (n2 / name :op1 "cancer"~e.28))))))
:purpose~e.19 (s / study-01~e.1
:ARG1 (a3 / affect-01~e.3
:ARG0~e.4 (k / knock-down-02~e.6
:ARG1 (p2 / protein
:name (n / name :op1 "MUC1"~e.5)))
:ARG1~e.7 (c2 / cell-line~e.10,11
:source (d2 / disease :wiki "Breast_cancer"
:name (n3 / name :op1 "breast"~e.8 :op2 "cancer"~e.9))))))
# ::id pmid_1684_6534.115 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Only genes with greater than two @-@ fold change were considered .
# ::alignments 0-1.2 1-1.1 2-1.1.1.r 3-1.1.1.1 3-1.1.1.1.1 3-1.1.1.1.1.r 4-1.1.1.1.2.r 5-1.1.1.1.2.1.1 7-1.1.1.1.2.1 8-1.1.1 8-1.1.1.1.2 10-1
(c / consider-02~e.10
:ARG1 (g / gene~e.1
:ARG1-of~e.2 (c2 / change-01~e.8
:ARG2 (g2 / great~e.3
:degree~e.3 (m / more~e.3)
:compared-to~e.4 (c3 / change-01~e.8
:ARG2 (p / product-of~e.7 :op1 2~e.5)))))
:mod (o / only~e.0))
# ::id pmid_1684_6534.116 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Three genes ( MAP2K1 , VEGF , PDGFA ) were altered two @-@ fold or more after MUC1 siRNA in both MDA @-@ MB @-@ 468 and BT @-@ 20 cells ( Figure 2 ) ; two genes ( ITGAV , MMP2 ) changed only in 468.siMUC1 ; and five genes ( TIMP3 , RAF1 , JUN , TNF , CDC25A ) only in BT.siMUC1 .
# ::alignments 0-1.1.1.1 1-1.1.1 4-1.1.1.2.1.1.1.1 8-1.1.1.2.1.2.1.1 12-1.1.1.2.1.3.1.1 16-1.1 17-1.1.2.1.1 19-1.1.2.1 20-1.1.2 21-1.1.2.2 22-1.1.3 23-1.1.3.1.2.1.1.1 24-1.1.3.1.1.1 27-1.1.4.1.1.1 29-1.1.4.1.1.1 31-1.1.4.1.1.1 32-1.1.4 33-1.1.4.2.1.1 35-1.1.4.2.1.1 36-1.1.4.1 36-1.1.4.2 36-1.2.3 36-1.3.3 38-1.1.5.1 40-1.1.5.1.1 44-1.2.1.1 45-1.2.1 48-1.2.1.2.1.1.1.1 52-1.2.1.2.1.2.1.1 55-1.2 55-1.3 56-1.2.2 58-1.2.3.1.1 60-1 61-1.3.1.1 62-1.3.1 65-1.3.1.2.1.1.1.1 69-1.3.1.2.1.2.1.1 73-1.3.1.2.1.3.1.1 77-1.3.1.2.1.4.1.1 81-1.3.1.2.1.5.1.1 84-1.3.2 86-1.3.3.1.1
(a6 / and~e.60
:op1 (a / alter-01~e.16
:ARG1 (g / gene~e.1 :quant 3~e.0
:ARG1-of (m2 / mean-01
:ARG2 (a2 / and
:op1 (g2 / gene
:name (n / name :op1 "MAP2K1"~e.4))
:op2 (g3 / gene
:name (n2 / name :op1 "VEGF"~e.8))
:op3 (g4 / gene
:name (n3 / name :op1 "PDGFA"~e.12)))))
:degree (o / or~e.20
:op1 (p / product-of~e.19 :op1 2~e.17)
:op2 (m3 / more-than~e.21
:op1 p))
:time (a3 / after~e.22
:op1 (n17 / nucleic-acid
:name (n4 / name :op1 "siRNA"~e.24)
:ARG0-of (e / encode-01
:ARG1 (p2 / protein
:name (n5 / name :op1 "MUC1"~e.23)))))
:location (a4 / and~e.32
:op1 (c / cell-line~e.36
:name (n6 / name :op1 "MDA-MB-468"~e.27,29,31))
:op2 (c2 / cell-line~e.36
:name (n7 / name :op1 "BT-20"~e.33,35)))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.38 :mod 2~e.40)))
:op2 (c3 / change-01~e.55
:ARG1 (g5 / gene~e.45 :quant 2~e.44
:ARG1-of (m4 / mean-01
:ARG2 (a5 / and
:op1 (g6 / gene
:name (n8 / name :op1 "ITGAV"~e.48))
:op2 (g7 / gene
:name (n9 / name :op1 "MMP2"~e.52)))))
:mod o2~e.56
:location (c5 / cell-line~e.36
:name (n15 / name :op1 "468.siMUC1"~e.58)))
:op3 (c4 / change-01~e.55
:ARG1 (g8 / gene~e.62 :quant 5~e.61
:ARG1-of (m / mean-01
:ARG2 (a7 / and
:op1 (g9 / gene
:name (n10 / name :op1 "TIMP3"~e.65))
:op2 (g10 / gene
:name (n11 / name :op1 "RAF1"~e.69))
:op3 (g11 / gene
:name (n12 / name :op1 "JUN"~e.73))
:op4 (g12 / gene
:name (n13 / name :op1 "TNF"~e.77))
:op5 (g13 / gene
:name (n14 / name :op1 "CDC25A"~e.81)))))
:mod (o2 / only~e.84)
:location (c6 / cell-line~e.36
:name (n16 / name :op1 "BT.siMUC1"~e.86))))
# ::id pmid_1684_6534.117 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok This list represents all genes affected greater than two @-@ fold after MUC1 siRNA , rather than a select group .
# ::alignments 0-1.1.1 1-1.1 2-1 3-1.2.1 4-1.2 5-1.2.2 6-1.2.2.1 6-1.2.2.1.1 6-1.2.2.1.1.r 7-1.2.2.1.2.r 8-1.2.2.1.2.1 10-1.2.2.1.2 11-1.2.2.2 12-1.2.2.2.1.2.1.1.1 13-1.2.2.2.1.1.1 15-1.3 16-1.2.2.1.2.r 18-1.3.1.1 19-1.3.1
(r / represent-01~e.2
:ARG0 (l / list~e.1
:mod (t / this~e.0))
:ARG1 (g / gene~e.4
:mod (a / all~e.3)
:ARG1-of (a2 / affect-01~e.5
:degree (g2 / great~e.6
:degree~e.6 (m / more~e.6)
:compared-to~e.7,16 (p / product-of~e.10 :op1 2~e.8))
:time (a3 / after~e.11
:op1 (n3 / nucleic-acid
:name (n / name :op1 "siRNA"~e.13)
:ARG0-of (e / encode-01
:ARG1 (p2 / protein
:name (n2 / name :op1 "MUC1"~e.12)))))))
:ARG1-of (i / instead-of-91~e.15
:ARG2 (g3 / group~e.19
:ARG1-of (s / select-01~e.18))))
# ::id pmid_1684_6534.118 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Three genes whose transcription was changed by less than two @-@ fold are shown , two of which ( PDGFB @ and ITGB1 ) are listed because they relate closely to genes altered by two @-@ fold ( PDGFA @ and ITGAV ) .
# ::alignments 0-1.1.1 1-1.1 3-1.1.2 5-1.1.2.1 6-1.1.2.1.1.r 7-1.1.2.1.1 8-1.1.2.1.1 9-1.1.2.1.1.1.1 11-1.1.2.1.1.1 13-1 15-1.1.2.1.1.1.1 16-1.1.2.1.1.1 20-1.1.3.1.2.1.1.1.1 22-1.1.3.1.2.1 24-1.1.3.1.2.1.2.1.1 28-1.1.3.1.3 29-1.1.3.1.3.1 30-1.1.3.1.3.1.1.1 31-1.1.3.1.3.1.1 32-1.1.3.1.3.1.1.3 34-1.1.3.1 34-1.1.3.1.3.1.1.2 35-1.1.3.1.3.1.1.2.1 37-1.1.2.1.1.1.1 37-1.1.3.1.1 39-1.1.2.1.1.1 42-1.1.3.1.3.1.1.2.2.1.1.1.1 44-1.1.3.1.3.1.1.2.2.1 46-1.1.3.1.3.1.1.2.2.1.2.1.1
(s / show-01~e.13
:ARG1 (g / gene~e.1 :quant 3~e.0
:ARG1-of (t / transcribe-01~e.3
:ARG1-of (c / change-01~e.5
:ARG2~e.6 (l / less-than~e.7,8
:op1 (p / product-of~e.11,16,39 :op1 2~e.9,15,37))))
:ARG2-of (i / include-91
:ARG1 (g2 / gene~e.34 :quant 2~e.37
:ARG1-of (m / mean-01
:ARG2 (a / and~e.22
:op1 (g3 / gene
:name (n / name :op1 "PDGFB"~e.20))
:op2 (g4 / gene
:name (n2 / name :op1 "ITGB1"~e.24))))
:ARG1-of (l2 / list-01~e.28
:ARG1-of (c2 / cause-01~e.29
:ARG0 (r / relate-01~e.31
:ARG1 g2~e.30
:ARG2 (g5 / gene~e.34
:ARG1-of (a2 / alter-01~e.35
:degree p)
:ARG1-of (m2 / mean-01
:ARG2 (a3 / and~e.44
:op1 (g6 / gene
:name (n3 / name :op1 "PDGFA"~e.42))
:op2 (g7 / gene
:name (n4 / name :op1 "ITGAV"~e.46)))))
:manner (c3 / close-10~e.32))))))))
# ::id pmid_1684_6534.119 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The third , MYC , is included because western blots confirmed a substantial change at the protein level ( Figure 3a ) that may reflect both transcriptional and post @-@ transcriptional regulation .
# ::alignments 1-1.1.1 1-1.1.1.1 1-1.1.1.1.r 4-1.1.2.1.1.1 8-1 9-1.2 10-1.2.1.1 11-1.2.1.1 12-1.2.1 14-1.2.1.2.2 15-1.2.1.2 16-1.2.1.2.1.r 18-1.2.1.2.1.1 19-1.2.1.2.1 21-1.2.1.2.3.1 23-1.2.1.2.3.1.1 27-1.2.1.2.4.2 28-1.2.1.2.4 30-1.2.1.2.4.1.2.1.1 31-1.2.1.2.4.1 32-1.2.1.2.4.1.2.1 34-1.2.1.2.4.1.2.1.1 35-1.2.1.2.4.1.1 35-1.2.1.2.4.1.2
(i / include-01~e.8
:ARG1 (g / gene
:ord (o / ordinal-entity~e.1 :value~e.1 3~e.1)
:ARG1-of (m / mean-01
:ARG2 (g2 / gene
:name (n / name :op1 "MYC"~e.4))))
:ARG1-of (c / cause-01~e.9
:ARG0 (c2 / confirm-01~e.12
:ARG0 (i2 / immunoblot-01~e.10,11)
:ARG1 (c3 / change-01~e.15
:ARG1~e.16 (l / level~e.19
:quant-of (p / protein~e.18))
:degree (s / substantial~e.14)
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.21 :mod "3a"~e.23))
:ARG1-of (r / reflect-01~e.28
:ARG2 (a / and~e.31
:op1 (r2 / regulate-01~e.35
:time (t2 / transcribe-01))
:op1 (r3 / regulate-01~e.35
:time (a2 / after~e.32
:op1 t2~e.30,34)))
:ARG1-of (p2 / possible-01~e.27))))))
# ::id pmid_1684_6534.120 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Interestingly , transcription of MAP2K1 @ was decreased in both cell lines after MUC1 siRNA .
# ::alignments 0-1.4 2-1.1 5-1.1.1.1.1 8-1 9-1.2.r 10-1.2.1 11-1.2 12-1.2 13-1.3 14-1.3.1.2.1.1.1 15-1.3.1.1.1
(d / decrease-01~e.8
:ARG1 (t / transcribe-01~e.2
:ARG1 (g / gene
:name (n / name :op1 "MAP2K1"~e.5)))
:location~e.9 (c / cell-line~e.11,12
:mod (b / both~e.10))
:time (a / after~e.13
:op1 (n4 / nucleic-acid
:name (n2 / name :op1 "siRNA"~e.15)
:ARG0-of (e / encode-01
:ARG1 (p / protein
:name (n3 / name :op1 "MUC1"~e.14)))))
:ARG2-of (i / interest-01~e.0))
# ::id pmid_1684_6534.121 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok This gene encodes MEK1 , one of the primary regulators of the ERK1 @/@ 2 MAPK pathway [ @ 33 @ ] , a network that has been linked several times to MUC1 [ @ 12 , 34 @ - @ 36 @ ] .
# ::alignments 0-1.1.1 1-1.1 2-1 3-1.2.1.1 8-1.2.2.1.2 9-1.2.2.1 9-1.2.2.1.1 9-1.2.2.1.1.r 10-1.2.2.1.1.1.r 12-1.2.2.1.1.1.1.1 14-1.2.2.1.1.1.1.1 15-1.2.2.1.1.1.1.2 16-1.2.2.1.1.1 19-1.2.2.2.1.1.1 24-1.2.2.1.1.1.2 28-1.2.2.1.1.1.2.1 29-1.2.2.1.1.1.2.1.2 30-1.2.2.1.1.1.2.1.2.r 31-1.2.2.1.1.1.2.1.1.r 32-1.2.2.1.1.1.2.1.1.1.1 35-1.2.2.1.1.1.2.1.3.1.1.1.1 39-1.2.2.1.1.1.2.1.3.1.2.1.1.1 43-1.2.2.1.1.1.2.1.3.1.2.1.1.2
(e / encode-01~e.2
:ARG0 (g / gene~e.1
:mod (t / this~e.0))
:ARG1 (e2 / enzyme
:name (n / name :op1 "MEK1"~e.3)
:ARG1-of (i / include-91
:ARG2 (m / molecular-physical-entity~e.9
:ARG0-of~e.9 (r / regulate-01~e.9
:ARG1~e.10 (p2 / pathway~e.16
:name (n2 / name :op1 "ERK1/2"~e.12,14 :op2 "MAPK"~e.15)
:mod (n3 / network~e.24
:ARG1-of (l / link-01~e.28
:ARG2~e.31 (p4 / protein
:name (n4 / name :op1 "MUC1"~e.32))
:frequency~e.30 (s / several~e.29)
:ARG1-of (d2 / describe-01
:ARG0 (a / and
:op1 (p5 / publication
:ARG1-of (c2 / cite-01 :ARG2 12~e.35))
:op2 (p6 / publication
:ARG1-of (c3 / cite-01
:ARG2 (v / value-interval :op1 34~e.39 :op2 36~e.43)))))))))
:mod (p / primary~e.8))
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c / cite-01 :ARG2 33~e.19))))))
# ::id pmid_1684_6534.122 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We examined MEK1 and MEK2 levels by western blot to confirm decreased protein in MUC1 siRNA @-@ treated cells ( Figure 3a ) , and found that not only were total MEK1 @/@ 2 levels lower in 468.siMUC1 and BT.siMUC1 compared to controls ( 0.48 and 0.68 relative to siLuc , respectively ) , but so were the basal amounts of active ( phosphorylated ) MEK1 @/@ 2 ( pMEK1 @/@ 2 ; 0.12 and 0.42 relative to siLuc , respectively ) .
# ::alignments 0-1.1.1 1-1.1 2-1.1.2.1.1.1.1 3-1.1.2 4-1.1.2.2.1.1.1 4-1.2.2.2.2.1.1.1 5-1.1.2.1 5-1.1.2.2 5-1.2.2.1.1 5-1.2.2.1.2 5-1.2.2.1.5.1.2 6-1.1.3.r 7-1.1.3 8-1.1.3 10-1.1.4 11-1.1.4.2.1 12-1.1.4.2 13-1.1.4.2.1.1.r 14-1.1.4.2.1.1.1.1.2.1.1.1 15-1.1.4.2.1.1.1.1.1.1 17-1.1.4.2.1.1.1 18-1.1.4.2.1.1 20-1.1.5.1 22-1.1.5.1.1 26-1 27-1.2 32-1.2.2.1.3 33-1.2.2.2.1.1.1.1 36-1.2.2.1.5.1.1 37-1.2.2.1.4 37-1.2.2.1.4.1 37-1.2.2.1.4.1.r 38-1.2.3.r 39-1.2.3.1.1.1 41-1.2.3.2.1.1 42-1.2.2.1.4.2.r 44-1.2.2.1.4.2 46-1.2.2.1.5.1.1.1 48-1.2.2.1.5.1.2.1 49-1.2.2.1.5.1.4 51-1.2.2.1.5.1.4.1.1.1 53-1.2.2.2.5.1.3 53-1.2.2.2.5.1.3.r 60-1.2.2.2.3 61-1.2.2.2.1 61-1.2.2.2.2 61-1.2.2.2.5.1.1 61-1.2.2.2.5.1.2 65-1.2.2.2.1.1.2.1.1 65-1.2.2.2.2.1.2.1.1 67-1.2.2.2.1.1.1.1 75-1.2.2.2.5.1.1.1 76-1.2.2.2.5.1 77-1.2.2.2.5.1.2.1 78-1.2.2.1.5.1.4 80-1.2.2.1.5.1.4.1.1.1 82-1.2.2.1.5.1.3
(a / and~e.26
:op1 (e / examine-01~e.1
:ARG0 (w / we~e.0)
:ARG1 (a2 / and~e.3
:op1 (l / level~e.5
:quant-of (e2 / enzyme
:name (n / name :op1 "MEK1"~e.2)))
:op2 (l2 / level~e.5
:quant-of (e3 / enzyme
:name (n2 / name :op1 "MEK2"~e.4))))
:manner~e.6 (i / immunoblot-01~e.7,8)
:purpose (c / confirm-01~e.10
:ARG0 w
:ARG1 (p / protein~e.12
:ARG1-of (d / decrease-01~e.11
:location~e.13 (c2 / cell~e.18
:ARG1-of (t2 / treat-04~e.17
:ARG2 (n11 / nucleic-acid
:name (n4 / name :op1 "siRNA"~e.15)
:ARG0-of (e4 / encode-01
:ARG1 (p2 / protein
:name (n5 / name :op1 "MUC1"~e.14)))))))))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.20 :mod "3a"~e.22)))
:op2 (f2 / find-01~e.27
:ARG0 w
:ARG1 (a3 / and
:op1 (a4 / and
:op1 (l3 / level~e.5
:quant-of e2)
:op2 (l4 / level~e.5
:quant-of e3)
:mod (t3 / total~e.32)
:ARG1-of (l5 / low-04~e.37
:degree~e.37 (m / more~e.37)
:compared-to~e.42 (c3 / control~e.44))
:ARG1-of (m2 / mean-01
:ARG2 (a14 / and
:op1 (l6 / level~e.36 :quant 0.48~e.46)
:op2 (l7 / level~e.5 :quant 0.68~e.48)
:manner r2~e.82
:ARG1-of (r3 / relative-05~e.49,78
:ARG3 (c6 / cell-line
:name (n8 / name :op1 "siLuc"~e.51,80)))
:mod t3)))
:op2 (a7 / and
:op1 (a8 / amount~e.61
:quant-of (e5 / enzyme
:name (n9 / name :op1 "MEK1"~e.33,67)
:ARG1-of (a10 / activate-01
:ARG1-of (m3 / mean-01
:ARG2 (p3 / phosphorylate-01~e.65
:ARG3 e5)))))
:op2 (a9 / amount~e.61
:quant-of (e6 / enzyme
:name (n10 / name :op1 "MEK2"~e.4)
:ARG1-of (a11 / activate-01
:ARG1-of (m5 / mean-01
:ARG2 (p4 / phosphorylate-01~e.65
:ARG3 e6)))))
:mod (b / basal~e.60)
:ARG1-of l5
:ARG1-of (m4 / mean-01
:ARG2 (a12 / and~e.76
:op1 (a6 / amount~e.61 :quant 0.12~e.75)
:op2 (a13 / amount~e.61 :quant 0.42~e.77)
:manner~e.53 (r2 / respective~e.53)
:ARG1-of r3
:mod b))))
:location~e.38 (a5 / and
:op1 (c4 / cell-line
:name (n6 / name :op1 "468.siMUC1"~e.39))
:op2 (c5 / cell-line
:name (n7 / name :op1 "BT.siMUC1"~e.41)))))
# ::id pmid_1684_6534.123 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Both 468.siMUC1 and BT.siMUC1 also showed reduced activation of ERK1 @/@ 2 ( dpERK1 @/@ 2 ; 0.21 and 0.27 relative to siLuc , respectively ) , as would be expected with diminished signaling through MEK1 @/@ 2 ; total ERK1 @/@ 2 levels remain unchanged .
# ::alignments 1-1.1.1.1.1.1 2-1.1.1 3-1.1.1.2.1.1 4-1.1.3 5-1.1 6-1.1.2.2 7-1.1.2 7-1.1.2.3.1.1 7-1.1.2.3.1.2 8-1.1.2.1.r 9-1.1.2.1.1.1.1 10-1.1.2.1 14-1.1.2.1 17-1.1.2.3.1.1.1 18-1.1.2.3.1 19-1.1.2.3.1.2.1 20-1.1.2.3.1.4 21-1.1.2.3.1.4.1.r 22-1.1.2.3.1.4.1.1.1 24-1.1.2.3.1.3 24-1.1.2.3.1.3.r 30-1.1.4 32-1.1.4.1.1.2 33-1.1.4.1.1 35-1.1.4.1.1.1.1.1.1 36-1.1.4.1.1.1 39-1.2.1.1 40-1.2.1.2 41-1.2.1.2 43-1.2.1 44-1.2 45-1.2.2 45-1.2.2.1 45-1.2.2.1.r
(m2 / multi-sentence
:snt1 (s / show-01~e.5
:ARG0 (a / and~e.2
:op1 (c3 / cell-line
:name (n7 / name :op1 "468.siMUC1"~e.1))
:op2 (c4 / cell-line
:name (n8 / name :op1 "BT.siMUC1"~e.3)))
:ARG1 (a3 / activate-01~e.7
:ARG1~e.8 (s2 / slash~e.10,14
:op1 (e / enzyme
:name (n / name :op1 "ERK1"~e.9))
:op2 (e2 / enzyme
:name (n2 / name :op1 "ERK2"))
:ARG3-of (p / phosphorylate-01
:mod (d3 / dual)))
:ARG1-of (r / reduce-01~e.6)
:ARG1-of (m / mean-01
:ARG2 (a4 / and~e.18
:op1 (a5 / activate-01~e.7 :degree 0.21~e.17)
:op2 (a6 / activate-01~e.7 :degree 0.27~e.19)
:manner~e.24 (r2 / respective~e.24)
:ARG1-of (r4 / relative-05~e.20
:ARG3~e.21 (c5 / cell-line
:name (n9 / name :op1 "siLuc"~e.22))))))
:mod (a2 / also~e.4)
:ARG1-of (e3 / expect-01~e.30
:ARG1-of (c / cause-01
:ARG0 (s3 / signal-07~e.33
:ARG0 (s4 / slash~e.36
:op1 (e4 / enzyme
:name (n3 / name :op1 "MEK1"~e.35))
:op2 (e5 / enzyme
:name (n4 / name :op1 "MEK2")))
:ARG1-of (d / diminish-01~e.32)))))
:snt2 (r3 / remain-01~e.44
:ARG1 (l2 / level~e.43
:mod (t / total~e.39)
:quant-of s2~e.40,41)
:ARG3 (c2 / change-01~e.45 :polarity~e.45 -~e.45)))
# ::id pmid_1684_6534.124 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok As both lines have high levels of EGFR and thus activate the MEK @-@ ERK cascade intensely when stimulated with EGF [ @ 37 @ ] , siRNA @-@ transfected cells were treated with EGF .
# ::alignments 0-1.3.1.3.1.4.r 1-1.3.1.1.1 2-1.3.1.1 3-1.3.1 4-1.3.1.2.1 5-1.3.1.2 6-1.3.1.2.2.r 7-1.3.1.2.2.1.1 9-1.3 10-1.3.1.3.1 12-1.3.1.3.1.2.1.1 14-1.3.1.3.1.2.1.1 16-1.3.1.3.1.3 17-1.3.1.3.1.4.r 18-1.3.1.3.1.4 19-1.3.1.3.1.4.2.r 20-1.3.1.3.1.4.2 23-1.3.2.1.1.1 27-1.1.1.1.1.1 29-1.1.1 30-1.1 32-1 33-1.2.r 34-1.2.1.1
(t / treat-04~e.32
:ARG1 (c / cell~e.30
:ARG1-of (t2 / transfect-01~e.29
:ARG2 (n5 / nucleic-acid
:name (n2 / name :op1 "siRNA"~e.27))))
:ARG2~e.33 (p3 / protein
:name (n3 / name :op1 "EGF"~e.34))
:ARG1-of (c2 / cause-01~e.9
:ARG0 (h / have-03~e.3
:ARG0 (c3 / cell-line~e.2
:mod (b / both~e.1))
:ARG1 (l / level~e.5
:ARG1-of (h2 / high-02~e.4)
:quant-of~e.6 (e / enzyme
:name (n / name :op1 "EGFR"~e.7)))
:ARG2-of (i / infer-01
:ARG1 (a / activate-01~e.10
:ARG0 c3
:ARG1 (p / pathway
:name (n4 / name :op1 "MEK-ERK"~e.12,14))
:manner (i2 / intense-02~e.16)
:time~e.0,17 (s2 / stimulate-01~e.18
:ARG1 c3
:ARG2~e.19 p3~e.20))))
:ARG1-of (d / describe-01
:ARG0 (p2 / publication
:ARG1-of (c5 / cite-01 :ARG2 37~e.23)))))
# ::id pmid_1684_6534.125 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Notably , MUC1 siRNA impairs this important oncogenic pathway in MDA @-@ MB @-@ 468 cells , as 468.siMUC1 display less pMEK1 @/@ 2 in response to EGF than do 468.siLuc ( Figure 3b ) .
# ::alignments 0-1.4 2-1.1.2.1.1.1 3-1.1.1.1 4-1 5-1.2.1 6-1.2.2 7-1.2.3 7-1.2.3.1.2.1 7-1.5 8-1.2 10-1.3.1.1 12-1.3.1.1 14-1.3.1.1 15-1.3 15-1.5.1.1 15-1.5.1.4.1 17-1.5.1.r 18-1.5.1.1.1.1 19-1.5.1 19-1.5.1.4 20-1.5.1.2.4 22-1.5.1.2 22-1.5.1.4.2 24-1.5.1.3.r 25-1.5.1.3 26-1.5.1.3.1.r 27-1.5.1.3.1.1.1 28-1.5.1.4.r 30-1.5.1.4.1.1.1 32-1.6.1 34-1.6.1.1
(i / impair-01~e.4
:ARG0 (n11 / nucleic-acid
:name (n / name :op1 "siRNA"~e.3)
:ARG0-of (e3 / encode-01
:ARG1 (p / protein
:name (n2 / name :op1 "MUC1"~e.2))))
:ARG1 (p2 / pathway~e.8
:mod (t / this~e.5)
:mod (i2 / important~e.6)
:ARG0-of (c / cause-01~e.7
:ARG1 (d4 / disease :wiki "Cancer"
:name (n10 / name :op1 "cancer"~e.7))))
:location (c3 / cell-line~e.15
:name (n3 / name :op1 "MDA-MB-468"~e.10,12,14))
:ARG1-of (n4 / notable-04~e.0)
:ARG1-of (c4 / cause-01~e.7
:ARG0~e.17 (d / display-01~e.19
:ARG0 (c5 / cell-line~e.15
:name (n8 / name :op1 "468.siMUC1"~e.18))
:ARG1 (s / slash~e.22
:op1 (e / enzyme
:name (n5 / name :op1 "MEK1"))
:op2 (e2 / enzyme
:name (n6 / name :op1 "MEK2"))
:ARG3-of (p3 / phosphorylate-01)
:quant (l / less~e.20))
:ARG2-of~e.24 (r2 / respond-01~e.25
:ARG1~e.26 (p4 / protein
:name (n7 / name :op1 "EGF"~e.27)))
:compared-to~e.28 (d2 / display-01~e.19
:ARG0 (c6 / cell-line~e.15
:name (n9 / name :op1 "468.siLuc"~e.30))
:ARG1 (s3 / slash~e.22
:op1 e
:op2 e2))))
:ARG1-of (d3 / describe-01
:ARG0 (f / figure~e.32 :mod "3b"~e.34)))
# ::id pmid_1684_6534.126 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Interestingly , EGF treatment of BT @-@ 20 cells results in slightly higher pMEK1 @/@ 2 levels in BT.siMUC1 compared to BT.siLuc .
# ::alignments 0-1.3 2-1.1.2.1.1 3-1.1 5-1.1.1.1.1 7-1.1.1.1.1 8-1.1.1 8-1.2.1.2 8-1.2.3 9-1 10-1.2.r 11-1.2.1.1.1 12-1.2.1 12-1.2.1.1 12-1.2.1.1.r 14-1.2.2 16-1.2 18-1.2.3.1.1 19-1.2.1.2.r 21-1.2.1.2.1.1
(r / result-01~e.9
:ARG1 (t / treat-04~e.3
:ARG1 (c / cell-line~e.8
:name (n2 / name :op1 "BT-20"~e.5,7))
:ARG2 (s / small-molecule
:name (n / name :op1 "EGF"~e.2)))
:ARG2~e.10 (l / level~e.16
:ARG1-of (h / high-02~e.12
:degree~e.12 (m / more~e.12
:degree (s2 / slight~e.11))
:compared-to~e.19 (c2 / cell-line~e.8
:name (n5 / name :op1 "BT.siLuc"~e.21)))
:quant-of (s3 / slash~e.14
:op1 (e / enzyme
:name (n3 / name :op1 "MEK1"))
:op2 (e2 / enzyme
:name (n4 / name :op1 "MEK2"))
:ARG3-of (p / phosphorylate-01))
:location (c3 / cell-line~e.8
:name (n6 / name :op1 "BT.siMUC1"~e.18)))
:ARG2-of (i / interest-01~e.0))
# ::id pmid_1684_6534.127 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Though this result seems paradoxical in light of decreased MAP2K1 @ transcription in BT.siMUC1 , it likely results from differential functions of Raf isoforms in combination with the increased RAF1 @ transcription ( Figure 2 ) and protein level ( Figure 3a ) in these cells .
# ::alignments 0-1 1-1.2.1.1.2 2-1.2.1.1 2-1.2.1.1.1 2-1.2.1.1.1.r 3-1.2 8-1.2.2.1 10-1.2.2.1.1.1.1.1 12-1.2.2.1.1 13-1.2.2.1.1.2.r 14-1.2.2.1.1.2.1.1 17-1.1 18-1.1.1 19-1.1.1.1.r 20-1.1.1.1.1.2 21-1.1.1.1.1 22-1.1.1.1.1.1.r 23-1.1.1.1.1.1.1.1 24-1.1.1.1.1.1.2 26-1.1.1.1 27-1.1.1.1.2.r 29-1.1.1.1.2.4 31-1.1.1.1.2.1.1.1.1 33-1.1.1.1.2.1 35-1.1.1.1.2.1.2.1 37-1.1.1.1.2.1.2.1.1 40-1.1.1.1.2 41-1.1.1.1.2.2.1 42-1.1.1.1.2.2 44-1.1.1.1.2.2.2.1 46-1.1.1.1.2.2.2.1.1 49-1.1.1.2.r 50-1.1.1.2 51-1.2.2.1.1.2
(h / have-concession-91~e.0
:ARG1 (l / likely-01~e.17
:ARG1 (r3 / result-01~e.18
:ARG1~e.19 (c / combine-01~e.26
:ARG1 (f / function-01~e.21
:ARG0~e.22 (e / enzyme
:name (n / name :op1 "Raf"~e.23)
:mod (i / isoform~e.24))
:mod (d2 / differential~e.20))
:ARG2~e.27 (a / and~e.40
:op1 (t4 / transcribe-01~e.33
:ARG1 (g2 / gene
:name (n4 / name :op1 "RAF1"~e.31))
:ARG1-of (d4 / describe-01
:ARG0 (f3 / figure~e.35 :mod 2~e.37)))
:op2 (l2 / level~e.42
:quant-of (p / protein~e.41)
:ARG1-of (d3 / describe-01
:ARG0 (f2 / figure~e.44 :mod "3a"~e.46)))
:location c3
:ARG1-of (i2 / increase-01~e.29)))
:ARG2~e.49 t~e.50))
:ARG2 (s / seem-01~e.3
:ARG1 (p2 / paradox
:domain (t / thing~e.2
:ARG2-of~e.2 (r / result-01~e.2)
:mod (t2 / this~e.1)))
:ARG1-of (c4 / cause-01
:ARG0 (d / decrease-01~e.8
:ARG1 (t3 / transcribe-01~e.12
:ARG1 (g / gene
:name (n2 / name :op1 "MAP2K1"~e.10))
:location~e.13 (c3 / cell-line~e.51
:name (n3 / name :op1 "BT.siMUC1"~e.14)))))))
# ::id pmid_1684_6534.128 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Specifically , B @-@ Raf is thought to be the main activator of MEK under normal conditions ; Raf @-@ 1 activates MEK in response to stimulus [ @ 38 @ ] .
# ::alignments 0-1.3 2-1.1.1.1.1.1 4-1.1.1.1.1.1 6-1.1 10-1.1.1.3 11-1.1.1 12-1.1.1.2.r 13-1.1.1.2.1.1 15-1.1.1.4 16-1.1.1.4.r 18-1.1.1.1.1.1 18-1.2.1.1.1 20-1.2.1.1.1 21-1.2 22-1.2.2 23-1.2.3.r 24-1.2.3 25-1.2.3.1.r 26-1.2.3.1 29-1.4.1.1.1
(a2 / and
:op1 (t2 / think-01~e.6
:ARG1 (a3 / activate-01~e.11
:ARG0 (e / enzyme
:name (n / name :op1 "B-Raf"~e.2,4,18))
:ARG1~e.12 (e3 / enzyme
:name (n3 / name :op1 "MEK"~e.13))
:mod (m / main~e.10)
:condition~e.16 (n4 / normal~e.15)))
:op2 (a4 / activate-01~e.21
:ARG0 (e4 / enzyme
:name (n5 / name :op1 "Raf-1"~e.18,20))
:ARG1 e3~e.22
:ARG2-of~e.23 (r / respond-01~e.24
:ARG1~e.25 (s / stimulus~e.26)))
:ARG1-of (s2 / specific-02~e.0)
:ARG1-of (d / describe-01
:ARG0 (p / publication
:ARG1-of (c / cite-01 :ARG2 38~e.29))))
# ::id pmid_1684_6534.129 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Thus , it appears that basal pMEK1 @/@ 2 levels are not greatly affected by Raf @-@ 1 overexpression in BT.siMUC1 cells , likely because MEK is regulated primarily by B @-@ Raf under normal growth conditions .
# ::alignments 0-1 3-1.2 4-1.2.1.r 5-1.2.1.3.2 7-1.2.1.3.1 9-1.2.1.3 11-1.2.1.1 11-1.2.1.1.r 12-1.2.1.4 13-1.2.1 14-1.2.1.2.r 15-1.2.1.2.1.1.1 17-1.2.1.2.1.1.1 18-1.2.1.2 19-1.2.1.2.2.r 20-1.2.1.2.2.1.1 21-1.2.1.2.2 23-1.1.3 24-1 25-1.1.2.1.1 27-1.1 28-1.1.4 28-1.1.4.r 29-1.1.1.r 30-1.1.1.1.1 32-1.1.1.1.1 34-1.1.5.1 35-1.1.5 36-1.1.5.r
(c2 / cause-01~e.0,24
:ARG0 (r / regulate-01~e.27
:ARG0~e.29 (e2 / enzyme
:name (n3 / name :op1 "B-Raf"~e.30,32))
:ARG1 (e5 / enzyme
:name (n / name :op1 "MEK"~e.25))
:ARG1-of (l2 / likely-01~e.23)
:manner~e.28 (p / primary~e.28)
:condition~e.36 (g2 / grow-01~e.35
:ARG1-of (n7 / normal-02~e.34)))
:ARG1 (a / appear-02~e.3
:ARG1~e.4 (a2 / affect-01~e.13 :polarity~e.11 -~e.11
:ARG0~e.14 (o / overexpress-01~e.18
:ARG1 (e / enzyme
:name (n2 / name :op1 "Raf-1"~e.15,17))
:location~e.19 (c / cell-line~e.21
:name (n6 / name :op1 "BT.siMUC1"~e.20)))
:ARG1 (l / level~e.9
:quant-of (s / slash~e.7
:op1 (e3 / enzyme
:name (n4 / name :op1 "MEK1"))
:op2 (e4 / enzyme
:name (n5 / name :op1 "MEK2"))
:ARG3-of (p2 / phosphorylate-01))
:mod (b / basal~e.5))
:extent (g / great~e.12))))
# ::id pmid_1684_6534.130 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In contrast , when the cells are stimulated ( EGF ) , increased Raf @-@ 1 levels in BT.siMUC1 leads to heightened pMEK1 @/@ 2 ( Figure 3b ) .
# ::alignments 1-1 3-1.1.3.r 5-1.1.3.1 7-1.1.3 9-1.1.3.2.1.1 12-1.1.1.3 13-1.1.1.1.1.1 15-1.1.1.1.1.1 16-1.1.1 17-1.1.1.2.r 18-1.1.1.2.1.1 19-1.1 20-1.1.2.r 21-1.1.2.4 23-1.1.2 26-1.2.1 28-1.2.1.1
(c / contrast-01~e.1
:ARG2 (l / lead-03~e.19
:ARG0 (l2 / level~e.16
:quant-of (e / enzyme
:name (n / name :op1 "Raf-1"~e.13,15))
:location~e.17 (c2 / cell-line
:name (n2 / name :op1 "BT.siMUC1"~e.18))
:ARG1-of (i / increase-01~e.12))
:ARG2~e.20 (s / slash~e.23
:op1 (e2 / enzyme
:name (n3 / name :op1 "MEK1"))
:op2 (e3 / enzyme
:name (n4 / name :op1 "MEK2"))
:ARG3-of (p / phosphorylate-01)
:ARG1-of (h / heighten-01~e.21))
:time~e.3 (s2 / stimulate-01~e.7
:ARG1 (c3 / cell~e.5)
:ARG2 (p2 / protein
:name (n5 / name :op1 "EGF"~e.9))))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.26 :mod "3b"~e.28)))
# ::id pmid_1684_6534.131 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok MUC1 siRNA increases apoptosis in MDA @-@ MB @-@ 468 but not BT @-@ 20
# ::alignments 1-1.1.1.2.1.1.1 2-1.1.1.1.1 3-1.1 3-1.2 4-1.1.2 5-1.1.3.r 6-1.1.3.1.1 8-1.1.3.1.1 10-1.1.3.1.1 11-1 12-1.2.1 12-1.2.1.r 13-1.2.4.1.1 15-1.2.4.1.1
(c / contrast-01~e.11
:ARG1 (i / increase-01~e.3
:ARG0 (n5 / nucleic-acid
:name (n / name :op1 "siRNA"~e.2)
:ARG0-of (e / encode-01
:ARG1 (p / protein
:name (n2 / name :op1 "MUC1"~e.1))))
:ARG1 (a / apoptosis~e.4)
:location~e.5 (c2 / cell-line
:name (n3 / name :op1 "MDA-MB-468"~e.6,8,10)))
:ARG2 (i2 / increase-01~e.3 :polarity~e.12 -~e.12
:ARG0 n5
:ARG1 a
:location (c3 / cell-line
:name (n4 / name :op1 "BT-20"~e.13,15))))
# ::id pmid_1684_6534.132 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We next examined whether MUC1 knockdown and its associated transcriptional alterations would affect overall cellular events .
# ::alignments 0-1.1 1-1.3 2-1 3-1.2.1 3-1.2.1.r 4-1.2.2.1.1.1.1 5-1.2.2.1 6-1.2.2 7-1.2.2.2.2.1 7-1.2.2.2.2.1.r 8-1.2.2.2.2 9-1.2.2.2.1 10-1.2.2.2 12-1.2 13-1.2.3.2 14-1.2.3.1 15-1.2.3
(e / examine-01~e.2
:ARG0 (w / we~e.0)
:ARG1 (a / affect-01~e.12 :mode~e.3 interrogative~e.3
:ARG0 (a2 / and~e.6
:op1 (k / knock-down-02~e.5
:ARG1 (p / protein
:name (n2 / name :op1 "MUC1"~e.4)))
:op2 (a3 / alter-01~e.10
:ARG1 (t / transcribe-01~e.9
:ARG1 p)
:ARG1-of (a4 / associate-01~e.8
:ARG2~e.7 k~e.7)))
:ARG1 (e2 / event~e.15
:mod (c / cell~e.14)
:mod (o / overall~e.13)))
:time (n / next~e.1))
# ::id pmid_1684_6534.133 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok As several of the genes shown in Figure 2 are important in regulating proliferation and survival , and because of the recently described role of MUC1 in modulating apoptosis in response to cellular stresses [ @ 20 , 21 , 24 @ ] , we first analyzed whether MUC1 siRNA would alter apoptosis in these lines .
# ::alignments 0-1.3.r 1-1.4.1.1.1.1 2-1.4.1.1.1.1.r 4-1.4.1.1.1 4-1.4.1.1.1.2.1 5-1.4.1.1.1.2.1.1 6-1.4.1.1.1.2.1.1.1.r 7-1.4.1.1.1.2.1.1.1 9-1.4.1.1.1.2.1.1.1.1 11-1.4.1.1.1.r 12-1.4.1.1 13-1.4.1.1.2.r 14-1.4.1.1.2 15-1.4.1.1.2.1.1 16-1.4.1.1.2.1 17-1.4.1.1.2.1.2 19-1.4.1 19-1.4.1.3.1 20-1.4 23-1.4.1.2.3.1 24-1.4.1.2.3 24-1.4.1.3 27-1.4.1.2.2.1 29-1.4.1.2.2 30-1.4.1.2.2.2 31-1.4.1.2.2.3.r 32-1.4.1.2.2.3 33-1.4.1.2.2.3.1.r 34-1.4.1.2.2.3.1.1 35-1.4.1.2.2.3.1 38-1.4.1.3.1.1.1.1 42-1.4.1.3.1.2.1.1 46-1.4.1.3.1.3.1.1 50-1.1 51-1.3 52-1 53-1.2.1 53-1.2.1.r 54-1.2.2.2.1.1.1 55-1.2.2.1.1 57-1.2 58-1.2.3 59-1.2.4.r 60-1.2.4.1 61-1.2.4
(a / analyze-01~e.52
:ARG0 (w / we~e.50)
:ARG1 (a2 / alter-01~e.57 :mode~e.53 interrogative~e.53
:ARG0 (n3 / nucleic-acid
:name (n / name :op1 "siRNA"~e.55)
:ARG0-of (e / encode-01
:ARG1 (p / protein
:name (n2 / name :op1 "MUC1"~e.54))))
:ARG1 (a3 / apoptosis~e.58)
:location~e.59 (c / cell-line~e.61
:mod (t / this~e.60)))
:time~e.0 (f / first~e.51)
:ARG1-of (c2 / cause-01~e.20
:ARG0 (a4 / and~e.19
:op1 (i / important~e.12
:domain~e.11 (g / gene~e.4
:quant~e.2 (s / several~e.1)
:ARG1-of (i2 / include-91
:ARG2 (g2 / gene~e.4
:ARG1-of (s2 / show-01~e.5
:medium~e.6 (f2 / figure~e.7 :mod 2~e.9)))))
:purpose~e.13 (r2 / regulate-01~e.14
:ARG1 (a5 / and~e.16
:op1 (p2 / proliferate-01~e.15)
:op2 (s3 / survive-01~e.17))))
:op2 (p3 / play-02
:ARG0 p
:ARG1 (m / modulate-01~e.29
:ARG0 p~e.27
:ARG1 a3~e.30
:ARG2-of~e.31 (r3 / respond-01~e.32
:ARG1~e.33 (s4 / stress~e.35
:mod (c3 / cell~e.34))))
:ARG1-of (d / describe-01~e.24
:time (r4 / recent~e.23)))
:ARG1-of (d2 / describe-01~e.24
:ARG0 (a6 / and~e.19
:op1 (p4 / publication
:ARG1-of (c4 / cite-01 :ARG2 20~e.38))
:op2 (p5 / publication
:ARG1-of (c5 / cite-01 :ARG2 21~e.42))
:op3 (p6 / publication
:ARG1-of (c6 / cite-01 :ARG2 24~e.46)))))))
# ::id pmid_1684_6534.134 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Although there was no change in basal apoptosis in either line ( Figure 4a ) , we observed that the cell lines responded differently when trypsinized for re @-@ plating 24 hours after transfection ( Figure 4b ) .
# ::alignments 0-1 3-1.2.1 3-1.2.1.r 4-1.2 5-1.2.2.r 6-1.2.2.1 7-1.2.2 8-1.2.3.r 9-1.2.3.1 10-1.2.3 12-1.2.4.1 14-1.2.4.1.1 18-1.1.1 19-1.1 20-1.1.2.r 22-1.1.2.1 23-1.1.2.1 24-1.1.2 25-1.2.1.r 26-1.1.2.3.3.r 26-1.1.2.3.r 32-1.1.2.3.3.2.1 33-1.1.2.3.3.2.2 34-1.1.2.3.3 35-1.1.2.3.3.1 37-1.1.3.1 39-1.1.3.1.1
(h2 / have-concession-91~e.0
:ARG1 (o / observe-01~e.19
:ARG0 (w / we~e.18)
:ARG1~e.20 (r / respond-01~e.24
:ARG0 c2~e.22,23
:ARG1-of (d2 / differ-01)
:time~e.26 (t2 / trypsinize-00
:ARG1 c2
:purpose (r2 / replate-00)
:time~e.26 (a2 / after~e.34
:op1 (t3 / transfect-01~e.35
:ARG1 c2)
:quant (t / temporal-quantity :quant 24~e.32
:unit (h / hour~e.33)))))
:ARG1-of (d3 / describe-01
:ARG0 (f2 / figure~e.37 :mod "4b"~e.39)))
:ARG2 (c / change-01~e.4 :polarity~e.3,25 -~e.3
:ARG1~e.5 (a / apoptosis~e.7
:mod (b / basal~e.6))
:location~e.8 (c2 / cell-line~e.10
:mod (e / either~e.9))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.12 :mod "4a"~e.14))))
# ::id pmid_1684_6534.135 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Interestingly , 468.siMUC1 cells show greater apoptosis after trypsinization than do 468.siLuc ( 49.8 % versus 34.0 % , respectively ) , while BT @-@ 20 cells from both siRNA treatments display similar levels of apoptosis ( around 22 %) .
# ::alignments 0-1.3 2-1.1.1.1.1 3-1.1.1 3-1.1.2.1.2 4-1.1 5-1.1.2.1 5-1.1.2.1.1 5-1.1.2.1.1.r 6-1.1.2 7-1.1.3 9-1.1.2.1.2.r 11-1.1.2.1.2.1.1 13-1.1.2.1.3.1.1 14-1.1.2.1.3.1 16-1.1.2.1.2.2.1.1 17-1.1.2.1.2.2.1 17-1.2.2.3.1 22-1 22-1.1.3.r 23-1.2.1.1.1 25-1.2.1.1.1 26-1.2.1 27-1.2.1.2.r 28-1.2.1.2.2 29-1.2.1.2.1.1.1 30-1.2.1.2 31-1.2 32-1.2.2.2 33-1.2.2 34-1.2.2.1.r 35-1.2.2.1 38-1.2.2.3.1.1
(c / contrast-01~e.22
:ARG1 (s / show-01~e.4
:ARG0 (c2 / cell-line~e.3
:name (n / name :op1 "468.siMUC1"~e.2))
:ARG1 (a / apoptosis~e.6
:mod (g / great~e.5
:degree~e.5 (m / more~e.5)
:compared-to~e.9 (c3 / cell-line~e.3
:name (n2 / name :op1 "468.siLuc"~e.11)
:ARG1-of (m3 / mean-01
:ARG2 (p2 / percentage-entity~e.17 :value 34.0~e.16)))
:ARG1-of (m2 / mean-01
:ARG2 (p / percentage-entity~e.14 :value 49.8~e.13))))
:time~e.22 (a2 / after~e.7
:op1 (t / trypsinize-00)))
:ARG2 (d / display-01~e.31
:ARG0 (c4 / cell-line~e.26
:name (n3 / name :op1 "BT-20"~e.23,25)
:source~e.27 (t2 / treat-04~e.30
:ARG2 (n5 / nucleic-acid
:name (n4 / name :op1 "siRNA"~e.29))
:mod (b / both~e.28)))
:ARG1 (l / level~e.33
:degree-of~e.34 a~e.35
:ARG1-of (r / resemble-01~e.32)
:ARG1-of (m4 / mean-01
:ARG2 (p3 / percentage-entity~e.17 :value 22~e.38))))
:ARG2-of (i / interest-01~e.0))
# ::id pmid_1684_6534.136 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To examine whether this phenomenon is specific to trypsin treatment or part of a general stress response involving MUC1 , we subjected cells to a panel of stresses and measured cell death .
# ::alignments 1-1.3 2-1.3.2.1 2-1.3.2.1.r 3-1.3.2.2.1 4-1.3.2.2.1 6-1.3.2.2 7-1.3.2.2.2.r 8-1.3.2.2.2.1.1.1 9-1.3.2.2.2 10-1.3.2 14-1.3.2.3.2.2 15-1.3.2.3.2.1 16-1.3.2.3.2 17-1.3.2.3.2.3 18-1.3.2.3.2.3.1.1.1 20-1.1.1 21-1.1 22-1.1.2 23-1.1.3.r 25-1.1.3 26-1.1.3.1.r 27-1.1.3.1 28-1 29-1.2 30-1.2.2.1 31-1.2.2
(a / and~e.28
:op1 (s / subject-01~e.21
:ARG0 (w / we~e.20)
:ARG1 (c / cell~e.22)
:ARG2~e.23 (p / panel~e.25
:consist-of~e.26 (s2 / stress~e.27)))
:op2 (m / measure-01~e.29
:ARG0 w
:ARG1 (d / die-01~e.31
:ARG1 c~e.30))
:purpose (e2 / examine-01~e.1
:ARG0 w
:ARG1 (o / or~e.10 :mode~e.2 interrogative~e.2
:op1 (s3 / specific-02~e.6
:ARG1 p2~e.3,4
:ARG2~e.7 (t2 / treat-04~e.9
:ARG2 (e / enzyme
:name (n / name :op1 "trypsin"~e.8))))
:op2 (p2 / phenomenon
:mod (t / this)
:subevent-of (r / respond-01~e.16
:ARG1 (s4 / stress~e.15)
:ARG1-of (g / general-02~e.14)
:ARG2-of (i / involve-01~e.17
:ARG1 (p3 / protein
:name (n2 / name :op1 "MUC1"~e.18))))))))
# ::id pmid_1684_6534.137 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In agreement with the patterns seen with trypsinization , BT.siLuc and BT.siMUC1 respond similarly to all treatments ( data not shown ) , while 468.siMUC1 die more readily than 468.siLuc in response to trypsin , G418 , hydrogen peroxide , or celecoxib , a chemotherapeutic that targets the cyclooxygenase @-@ 2 ( COX @-@ 2 ) pathway ( Figure 4c ) ; these data were confirmed with two independent siRNA constructs ( data not shown ) .
# ::alignments 1-1.1.4 2-1.1.4.1.r 4-1.1.4.1 5-1.1.4.1.1 9-1.1.1.1.1.1.1 10-1.1.1.1 11-1.1.1.1.2.1.1 12-1.1.1 13-1.1.1.3 14-1.1.1.2.r 15-1.1.1.2.1 16-1.1.1.2 18-1.1.1.4.1 19-1.1.1.4.1.1.1 19-1.1.1.4.1.1.1.r 20-1.1.1.4.1.1 23-1.1 23-1.1.4.1.1.1.r 24-1.1.2.1.1.1 25-1.1.2 26-1.1.2.2.1 27-1.1.2.2 28-1.1.2.2.2.r 29-1.1.2.2.2.1.1 30-1.1.2.3.r 31-1.1.2.3 32-1.1.2.3.1.r 33-1.1.2.3.1.1.1.1 35-1.1.2.3.1.2.1.1 37-1.1.2.3.1.3.1.1 38-1.1.2.3.1.3.1.2 40-1.1.2.3.1 41-1.1.2.3.1.4.1.1 44-1.1.2.3.1.4.2.1 46-1.1.2.3.1.4.2 46-1.1.2.3.1.4.2.2 46-1.1.2.3.1.4.2.2.r 48-1.1.2.3.1.4.2.2.1.1.1 50-1.1.2.3.1.4.2.2.1.1.1 54-1.1.2.3.1.4.2.2.1.1.1 56-1.1.2.3.1.4.2.2.1 58-1.1.3.1 60-1.1.3.1.1 64-1.2.2.1 65-1.2.2 67-1.2 68-1.2.1.r 69-1.2.1.1 70-1.2.1.3 70-1.2.1.3.1 70-1.2.1.3.1.r 71-1.2.1.2.1.1 72-1.2.1 74-1.2.3.1 75-1.2.3.1.1.1 75-1.2.3.1.1.1.r 76-1.2.3.1.1
(m / multi-sentence
:snt1 (c / contrast-01~e.23
:ARG1 (r / respond-01~e.12
:ARG0 (a / and~e.10
:op1 (c2 / cell-line
:name (n2 / name :op1 "BT.siLuc"~e.9))
:op2 (c3 / cell-line
:name (n3 / name :op1 "BT.siMUC1"~e.11)))
:ARG1~e.14 (t / treat-04~e.16
:mod (a2 / all~e.15))
:ARG1-of (r2 / resemble-01~e.13)
:ARG1-of (d / describe-01
:ARG0 (d2 / data~e.18
:ARG1-of (s / show-01~e.20 :polarity~e.19 -~e.19))))
:ARG2 (d3 / die-01~e.25
:ARG1 (c4 / cell-line
:name (n4 / name :op1 "468.siMUC1"~e.24))
:manner (r3 / ready-02~e.27
:degree (m2 / more~e.26)
:compared-to~e.28 (c5 / cell-line
:name (n5 / name :op1 "468.siLuc"~e.29)))
:ARG2-of~e.30 (r4 / respond-01~e.31
:ARG1~e.32 (o / or~e.40
:op1 (e / enzyme
:name (n / name :op1 "trypsin"~e.33))
:op2 (s2 / small-molecule
:name (n6 / name :op1 "G418"~e.35))
:op3 (s3 / small-molecule
:name (n7 / name :op1 "hydrogen"~e.37 :op2 "peroxide"~e.38))
:op4 (s4 / small-molecule
:name (n8 / name :op1 "celecoxib"~e.41)
:mod (s5 / small-molecule~e.46
:mod (c6 / chemotherapy~e.44)
:ARG0-of~e.46 (t2 / target-01~e.46
:ARG1 (p / pathway~e.56
:name (n9 / name :op1 "cyclooxygenase-2"~e.48,50,54))))))))
:ARG1-of (d4 / describe-01
:ARG0 (f / figure~e.58 :mod "4c"~e.60))
:ARG0-of (a3 / agree-01~e.1
:ARG2~e.2 (p2 / pattern~e.4
:ARG1-of (s7 / see-01~e.5
:time~e.23 (t4 / trypsinize-00)))))
:snt2 (c7 / confirm-01~e.67
:ARG0~e.68 (c8 / construct~e.72 :quant 2~e.69
:mod (n11 / nucleic-acid
:name (n10 / name :op1 "siRNA"~e.71))
:ARG0-of (d6 / depend-01~e.70 :polarity~e.70 -~e.70))
:ARG1 (d5 / data~e.65
:mod (t3 / this~e.64))
:ARG1-of (d7 / describe-01
:ARG0 (d8 / data~e.74
:ARG1-of (s6 / show-01~e.76 :polarity~e.75 -~e.75)))))
# ::id pmid_1684_6534.138 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Like the MAPK pathway , AKT signaling has been linked to MUC1 in cancer .
# ::alignments 0-1.3 2-1.3.1.1.1 3-1.3.1 5-1.1.1.1.1 6-1.1 9-1 10-1.2.r 11-1.2.1.1 12-1.4.r 13-1.4.2.1
(l / link-01~e.9
:ARG1 (s / signal-07~e.6
:ARG0 (e / enzyme
:name (n3 / name :op1 "AKT"~e.5)))
:ARG2~e.10 (p2 / protein
:name (n4 / name :op1 "MUC1"~e.11))
:ARG1-of (r / resemble-01~e.0
:ARG2 (p / pathway~e.3
:name (n / name :op1 "MAPK"~e.2)))
:location~e.12 (d / disease :wiki "Cancer"
:name (n2 / name :op1 "cancer"~e.13)))
# ::id pmid_1684_6534.139 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Although transcription of AKT @ was not altered in MUC1 siRNA @-@ treated cells , the results of our apoptosis studies prompted us to investigate levels of AKT further .
# ::alignments 0-1 1-1.2.2 4-1.2.2.1.1.1 7-1.2.1 7-1.2.1.r 8-1.2 9-1.2.3.r 10-1.2.3.1.1.2.1.1.1 11-1.2.3.1.1.1.1 13-1.2.3.1 14-1.2.3 17-1.1.1 17-1.1.1.1 17-1.1.1.1.r 18-1.1.1.1.1.r 19-1.1.1.1.1.1 19-1.1.1.1.1.1.r 20-1.1.1.1.1.2 21-1.1.1.1.1 22-1.1 23-1.1.3.1 25-1.1.3 26-1.1.3.2 27-1.1.3.2.1.r 28-1.1.3.2.1.1.1 29-1.1.3.3
(h / have-concession-91~e.0
:ARG1 (p / prompt-02~e.22
:ARG0 (t / thing~e.17
:ARG2-of~e.17 (r / result-01~e.17
:ARG1~e.18 (s / study-01~e.21
:ARG0~e.19 (w / we~e.19)
:ARG1 (a / apoptosis~e.20))))
:ARG1 w
:ARG2 (i / investigate-01~e.25
:ARG0 w~e.23
:ARG1 (l / level~e.26
:quant-of~e.27 (e / enzyme
:name (n2 / name :op1 "AKT"~e.28)))
:degree (f / further~e.29)))
:ARG2 (a2 / alter-01~e.8 :polarity~e.7 -~e.7
:ARG1 (t2 / transcribe-01~e.1
:ARG1 (g / gene
:name (n / name :op1 "AKT"~e.4)))
:location~e.9 (c / cell~e.14
:ARG1-of (t3 / treat-04~e.13
:ARG2 (n5 / nucleic-acid
:name (n3 / name :op1 "siRNA"~e.11)
:ARG0-of (e2 / encode-01
:ARG1 (p2 / protein
:name (n4 / name :op1 "MUC1"~e.10))))))))
# ::id pmid_1684_6534.140 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok As expected , the total AKT protein level is not greatly changed after MUC1 siRNA in either cell line , though the active form ( pAKT ) is increased in both 468.siMUC1 and BT.siMUC1 compared to controls ( Figure 3a ) .
# ::alignments 0-1.4.r 1-1.7 4-1.2.1 5-1.2.2.1.1 6-1.4.1.2.1 7-1.2 9-1.1 9-1.1.r 10-1.3 11-1 12-1.4 13-1.4.1.2.1.1.1 14-1.4.1.1.1 15-1.5.r 16-1.5.1 17-1.5 18-1.5 20-1.8.r 23-1.8.1 25-1.8.1.3.1.1.1 25-1.8.1.3.1.2 28-1.8 31-1.8.2.1.1.1 32-1.8.2 33-1.8.2.2.1.1 34-1.8.3.r 36-1.8.3 38-1.6.1 40-1.6.1.1
(c / change-01~e.11 :polarity~e.9 -~e.9
:ARG1 (l / level~e.7
:mod (t / total~e.4)
:quant-of (e4 / enzyme
:name (n / name :op1 "AKT"~e.5)))
:degree (g / great~e.10)
:time~e.0 (a / after~e.12
:op1 (n7 / nucleic-acid
:name (n2 / name :op1 "siRNA"~e.14)
:ARG0-of (e3 / encode-01
:ARG1 (p2 / protein~e.6
:name (n3 / name :op1 "MUC1"~e.13)))))
:location~e.15 (c2 / cell-line~e.17,18
:mod (e / either~e.16))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.38 :mod "3a"~e.40))
:ARG1-of (e2 / expect-01~e.1)
:concession~e.20 (i / increase-01~e.28
:ARG1 (f2 / form~e.23
:mod e4
:ARG1-of (a2 / activate-01)
:ARG1-of (m / mean-01
:ARG2 (e5 / enzyme
:name (n6 / name :op1 "AKT"~e.25)
:ARG3-of (p5 / phosphorylate-01~e.25))))
:location (a3 / and~e.32
:op1 (c3 / cell-line
:name (n4 / name :op1 "468.siMUC1"~e.31))
:op2 (c4 / cell-line
:name (n5 / name :op1 "BT.siMUC1"~e.33)))
:compared-to~e.34 (c5 / control~e.36)))
# ::id pmid_1684_6534.141 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok This result disagrees with MUC1 activation of the AKT pathway in rat 3Y1 cells [ @ 18 @ ] , and may reflect regulation more appropriate to breast cancer cells ; this is supported by activation of AKT in response to MUC1 siRNA in other lines [ @ 21 @ ] .
# ::alignments 0-1.1.1.1 1-1.1.1 1-1.1.1.2 1-1.1.1.2.r 2-1.1 3-1.1.2.r 4-1.1.2.1.1.1 5-1.1.2 6-1.1.2.2.r 8-1.1.2.2.1.1 9-1.1.2.2 10-1.1.2.3.r 11-1.1.2.3.2 12-1.1.2.3.1.1 13-1.1.2.3 16-1.1.3.1.1.1 20-1 21-1.2 22-1.2.1 23-1.2.1.2 24-1.2.1.2.1.2 25-1.2.1.2.1 26-1.2.1.2.1.1.r 27-1.2.1.2.1.1.1.2.1 28-1.2.1.2.1.1.1.2.2 29-1.2.1.2.1.1 31-1.2.1.1 33-1.3 34-1.3.1.r 35-1.3.1 36-1.3.1.1.r 37-1.3.1.1 38-1.3.1.2.r 39-1.3.1.2 41-1.1.2.1.1.1 42-1.3.1.2.1.1.1 43-1.3.1.3.r 44-1.3.1.3.1 45-1.3.1.3 48-1.3.2.1.1.1
(a / and~e.20
:op1 (d3 / disagree-01~e.2
:ARG0 (t / thing~e.1
:mod (t2 / this~e.0)
:ARG2-of~e.1 (r / result-01~e.1))
:ARG1~e.3 (a2 / activate-01~e.5
:ARG0 (p / protein
:name (n2 / name :op1 "MUC1"~e.4,41))
:ARG1~e.6 (p2 / pathway~e.9
:name (n3 / name :op1 "AKT"~e.8))
:location~e.10 (c / cell~e.13
:name (n4 / name :op1 "3Y1"~e.12)
:source (r2 / rat~e.11)))
:ARG1-of (d4 / describe-01
:ARG0 (p3 / publication
:ARG1-of (c2 / cite-01 :ARG2 18~e.16))))
:op2 (p4 / possible-01~e.21
:ARG1 (r3 / reflect-01~e.22
:ARG1 t~e.31
:ARG2 (r4 / regulate-01~e.23
:ARG1-of (a3 / appropriate-02~e.25
:ARG2~e.26 (c3 / cell~e.29
:source (d2 / disease :wiki "Breast_cancer"
:name (n / name :op1 "breast"~e.27 :op2 "cancer"~e.28)))
:degree (m / more~e.24)))))
:ARG1-of (s / support-01~e.33
:ARG0~e.34 (a4 / activate-01~e.35
:ARG1~e.36 p2~e.37
:ARG2-of~e.38 (r5 / respond-01~e.39
:ARG1 (n6 / nucleic-acid
:name (n5 / name :op1 "siRNA"~e.42)
:ARG0-of (e / encode-01
:ARG1 p)))
:location~e.43 (c5 / cell-line~e.45
:mod (o / other~e.44)))
:ARG1-of (d / describe-01
:ARG0 (p5 / publication
:ARG1-of (c6 / cite-01 :ARG2 21~e.48)))))
# ::id pmid_1684_6534.142 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In addition , there is a striking difference in the relative amounts of AKT and pAKT in the two cell lines ( Figure 4d ) .
# ::alignments 0-1.1.1 1-1 1-1.1.1 6-1.1.2 7-1.1 10-1.1.1.1.1 11-1.1.1.1 11-1.1.1.2 13-1.1.1.1.2.1.1 13-1.1.1.2.2.1.1 14-1.1.1 15-1.1.1.2.2.2 16-1.1.3.r 18-1.1.3.1 19-1.1.3 20-1.1.3 22-1.1.4.1 24-1.1.4.1.1
(a4 / and~e.1
:op2 (d / differ-02~e.7
:ARG1 (a2 / and~e.0,1,14
:op1 (a / amount~e.11
:ARG1-of (r / relative-05~e.10)
:quant-of (e / enzyme
:name (n / name :op1 "AKT"~e.13)))
:op2 (a3 / amount~e.11
:ARG1-of r
:quant-of (e2 / enzyme
:name (n2 / name :op1 "AKT"~e.13)
:ARG3-of (p / phosphorylate-01~e.15))))
:ARG0-of (s / strike-01~e.6)
:location~e.16 (c / cell-line~e.19,20 :quant 2~e.18)
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.22 :mod "4d"~e.24))))
# ::id pmid_1684_6534.143 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok When lysates from both lines are exposed to film for the same length of time ( overexposure masks the differences between BT.siLuc and BT.siMUC1 that are apparent in Figure 3a ) , it is clear that pAKT levels are much higher in BT @-@ 20 than in MDA @-@ MB @-@ 468 , despite lower total AKT expression .
# ::alignments 0-1.2.r 1-1.2.1 2-1.2.1.1.r 4-1.1.3 4-1.1.4 4-1.2.4.1.2.1 4-1.2.4.1.2.2 6-1.2 7-1.2.2.r 8-1.2.2 11-1.2.3 12-1.2.3.r 14-1.2.r 17-1.2.4.1 19-1.2.4.1.2 21-1.2.4.1.2.1.1.1 23-1.2.4.1.2.2.1.1 26-1.2.4.1.2.3 27-1.2.4.1.2.3.1.r 28-1.2.4.1.2.3.1 30-1.2.4.1.2.3.1.1 36-1 37-1.1.r 38-1.1.1.1.1.1 38-1.1.1.1.2 39-1.1.1 41-1.1.2.1 42-1.1 42-1.1.2 42-1.1.2.r 44-1.1.3.1.1 46-1.1.3.1.1 47-1.1.4.r 49-1.1.4.1.1 51-1.1.4.1.1 53-1.1.4.1.1 55-1.3.r 56-1.3.3 56-1.3.3.1 56-1.3.3.1.r 57-1.3.2 58-1.3.1 59-1.3
(c / clear-06~e.36
:ARG1~e.37 (h2 / high-02~e.42
:ARG1 (l2 / level~e.39
:quant-of (e / enzyme
:name (n / name :op1 "AKT"~e.38)
:ARG3-of (p / phosphorylate-01~e.38)))
:degree~e.42 (m / more~e.42
:quant (m3 / much~e.41))
:location (c2 / cell-line~e.4
:name (n2 / name :op1 "BT-20"~e.44,46))
:compared-to~e.47 (c3 / cell-line~e.4
:name (n3 / name :op1 "MDA-MB-468"~e.49,51,53)))
:time~e.0,14 (e3 / expose-01~e.6
:ARG1 (l3 / lysate~e.1
:source~e.2 (a / and
:op1 c2
:op2 c3))
:ARG2~e.7 (f / film~e.8)
:duration~e.12 (s / same-01~e.11)
:ARG1-of (m4 / mean-01
:ARG2 (m5 / mask-01~e.17
:ARG0 (o / overexpose-00
:ARG1 l3)
:ARG1 (d / differ-02~e.19
:ARG1 (c4 / cell-line~e.4
:name (n4 / name :op1 "BT.siLuc"~e.21))
:ARG2 (c5 / cell-line~e.4
:name (n5 / name :op1 "BT.siMUC1"~e.23))
:ARG1-of (a2 / appear-02~e.26
:medium~e.27 (f2 / figure~e.28 :mod "3a"~e.30))))))
:concession~e.55 (e2 / express-03~e.59
:ARG2 e~e.58
:degree (t / total~e.57)
:ARG1-of (l / low-04~e.56
:degree~e.56 (m2 / more~e.56))))
# ::id pmid_1684_6534.144 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok This difference in AKT activation between MDA @-@ MB @-@ 468 and BT @-@ 20 likely contributes to the disparity in their sensitivity to the increased apoptosis expected with loss of MUC1 .
# ::alignments 0-1.1.1.4 1-1.1.1 2-1.1.1.3.r 3-1.1.1.3.1.1.1 4-1.1.1.3 6-1.1.1.1.1.1 8-1.1.1.1.1.1 10-1.1.1.1.1.1 12-1.1.1.2.1.1 14-1.1.1.2.1.1 15-1 16-1.1 17-1.1.2.r 19-1.1.2 22-1.1.2.1 23-1.1.2.1.2.r 25-1.1.2.1.2.1 26-1.1.2.1.2 27-1.1.2.1.2.2 28-1.1.2.1.2.2.1.r 29-1.1.2.1.2.2.1 30-1.1.2.1.2.2.1.1.r 31-1.1.2.1.2.2.1.1.1.1
(l / likely-01~e.15
:ARG1 (c / contribute-01~e.16
:ARG0 (d / differ-02~e.1
:ARG1 (c3 / cell-line
:name (n2 / name :op1 "MDA-MB-468"~e.6,8,10))
:ARG2 (c2 / cell-line
:name (n3 / name :op1 "BT-20"~e.12,14))
:ARG3~e.2 (a / activate-01~e.4
:ARG1 (e / enzyme
:name (n / name :op1 "AKT"~e.3)))
:mod (t / this~e.0))
:ARG2~e.17 (d2 / disparity~e.19
:domain (s / sensitive-03~e.22
:ARG0 (a3 / and
:op1 c3
:op2 c2)
:ARG1~e.23 (a2 / apoptosis~e.26
:ARG1-of (i / increase-01~e.25)
:ARG1-of (e2 / expect-01~e.27
:time~e.28 (l2 / lose-02~e.29
:ARG1~e.30 (p / protein
:name (n4 / name :op1 "MUC1"~e.31)))))))))
# ::id pmid_1684_6534.145 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok MUC1 siRNA alters proliferation and invasion
# ::alignments 1-1.1.2.1.1.1 2-1.1.1.1 3-1 4-1.2.1 5-1.2 6-1.2.2
(a / alter-01~e.3
:ARG0 (n3 / nucleic-acid
:name (n / name :op1 "siRNA"~e.2)
:ARG0-of (e / encode-01
:ARG1 (p2 / protein
:name (n2 / name :op1 "MUC1"~e.1))))
:ARG1 (a2 / and~e.5
:op1 (p / proliferate-01~e.4)
:op2 (i / invade-01~e.6)))
# ::id pmid_1684_6534.146 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok As MUC1 is involved in apoptosis , we next analyzed its effects on proliferation .
# ::alignments 0-1.2.3.r 1-1.1.1.1.1 3-1.1 4-1.1.2.r 5-1.1.2 7-1.2.1 8-1.2.3 9-1.2 10-1.2.2.1 10-1.2.2.1.r 11-1.2.2 12-1.2.2.2.r 13-1.2.2.2
(c / cause-01
:ARG0 (i / involve-01~e.3
:ARG1 (p2 / protein
:name (n2 / name :op1 "MUC1"~e.1))
:ARG2~e.4 (a3 / apoptosis~e.5))
:ARG1 (a / analyze-01~e.9
:ARG0 (w / we~e.7)
:ARG1 (a2 / affect-01~e.11
:ARG0~e.10 p2~e.10
:ARG1~e.12 (p / proliferate-01~e.13))
:time~e.0 (n / next~e.8)))
# ::id pmid_1684_6534.147 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok BrdU and [ @ 3 @ H]thymidine incorporation were used to analyze proliferation after MUC1 siRNA .
# ::alignments 0-1.1.1.1.1.1 1-1.1 7-1.1.1 7-1.1.2 9-1 11-1.2 12-1.2.1 13-1.3 14-1.3.1.2.1.1.1 15-1.3.1.1.1
(u / use-01~e.9
:ARG1 (a / and~e.1
:op1 (i / incorporate-02~e.7
:ARG1 (s2 / small-molecule
:name (n / name :op1 "BrdU"~e.0)))
:op2 (i2 / incorporate-02~e.7
:ARG1 (s / small-molecule
:name (n2 / name :op1 "3H-thymidine"))))
:ARG2 (a2 / analyze-01~e.11
:ARG1 (p / proliferate-01~e.12))
:time (a3 / after~e.13
:op1 (n5 / nucleic-acid
:name (n3 / name :op1 "siRNA"~e.15)
:ARG0-of (e / encode-01
:ARG1 (p3 / protein
:name (n4 / name :op1 "MUC1"~e.14))))))
# ::id pmid_1684_6534.148 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok 468.siMUC1 cells show a significant decrease in [ @ 3 @ H]thymidine incorporation compared to 468.siLuc , while intriguingly , BT.siMUC1 cells show a significant increase in proliferation ( Figure 5a ) .
# ::alignments 0-1.1.1.1.1 1-1.1.1 2-1.1 2-1.1.3 4-1.1.2.2 5-1.1.2 12-1.1.2.1 13-1.1.3.r 15-1.1.3.1.1.1 17-1 18-1.2.3 20-1.2.1.1.1 21-1.1.1 21-1.1.3.1 21-1.2.1 22-1.1 22-1.1.3 22-1.2 24-1.2.2.2 25-1.2.2 26-1.2.2.1.r 27-1.2.2.1 29-1.3.1 31-1.3.1.1
(c / contrast-01~e.17
:ARG1 (s / show-01~e.2,22
:ARG0 (c3 / cell-line~e.1,21
:name (n / name :op1 "468.siMUC1"~e.0))
:ARG1 (d2 / decrease-01~e.5
:ARG1 (i / incorporate-02~e.12
:ARG1 (s5 / small-molecule
:name (n3 / name :op1 "3H-thymidine")))
:ARG1-of (s3 / significant-02~e.4))
:compared-to~e.13 (s2 / show-01~e.2,22
:ARG0 (c2 / cell-line~e.21
:name (n2 / name :op1 "468.siLuc"~e.15))))
:ARG2 (s4 / show-01~e.22
:ARG0 (c4 / cell-line~e.21
:name (n4 / name :op1 "BT.siMUC1"~e.20))
:ARG1 (i2 / increase-01~e.25
:ARG1~e.26 (p / proliferate-01~e.27)
:ARG1-of s3~e.24)
:ARG0-of (i3 / intrigue-01~e.18))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.29 :mod "5a"~e.31)))
# ::id pmid_1684_6534.149 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Growth curves mirror these results , as do experiments with the two independent MUC1 siRNA oligonucleotides ( data not shown ) .
# ::alignments 0-1.2.1 1-1.2 2-1 2-1.3.1 3-1.1.2 4-1.1 4-1.1.1 4-1.1.1.r 8-1.3.1.1 9-1.3.1.1.1.r 11-1.3.1.1.1.1 12-1.3.1.1.1.3 12-1.3.1.1.1.3.1 12-1.3.1.1.1.3.1.r 13-1.3.1.1.1.2.2.1.1.1 14-1.3.1.1.1.2.1.1 15-1.3.1.1.1 17-1.4.1 18-1.4.1.1.1 18-1.4.1.1.1.r 19-1.4.1.1
(m / mirror-01~e.2
:ARG1 (t / thing~e.4
:ARG2-of~e.4 (r / result-01~e.4)
:mod (t2 / this~e.3))
:ARG2 (c / curve-01~e.1
:ARG1 (g / grow-01~e.0))
:ARG1-of (r3 / resemble-01
:ARG2 (m2 / mirror-01~e.2
:ARG2 (e2 / experiment-01~e.8
:ARG1~e.9 (o / oligonucleotide~e.15 :quant 2~e.11
:mod (n3 / nucleic-acid
:name (n2 / name :op1 "siRNA"~e.14)
:ARG0-of (e / encode-01
:ARG1 (p / protein
:name (n / name :op1 "MUC1"~e.13))))
:ARG0-of (d / depend-01~e.12 :polarity~e.12 -~e.12)))))
:ARG1-of (d2 / describe-01
:ARG0 (d3 / data~e.17
:ARG1-of (s / show-01~e.19 :polarity~e.18 -~e.18))))
# ::id pmid_1684_6534.150 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Note that these assays require trypsinizing cells 24 hours post @-@ transfection ; therefore , the results in the MDA @-@ MB @-@ 468 line could stem from the changes in apoptosis described in the previous section , rather than a true effect on proliferation .
# ::alignments 0-1.1 1-1.1.1.r 2-1.1.1.1.1 3-1.1.1.1 4-1.1.1 6-1.1.1.2.1 7-1.1.1.2.2.2.1 8-1.1.1.2.2.2.2 9-1.1.1.2.2 11-1.1.1.2.2.1 13-1.2 16-1.2.1.1.1.1 16-1.2.1.1.1.1.1 16-1.2.1.1.1.1.1.r 17-1.2.1.1.1.1.2.r 19-1.2.1.1.1.1.2.1.1 21-1.2.1.1.1.1.2.1.1 23-1.2.1.1.1.1.2.1.1 24-1.2.1.1.1.1.2 25-1.2.1 26-1.2.1.1.1 27-1.2.1.1.1.2.r 29-1.2.1.1.1.2 30-1.2.1.1.1.2.1.r 31-1.2.1.1.1.2.1 32-1.2.1.1.1.2.2 33-1.2.1.1.1.2.2.1.r 35-1.2.1.1.1.2.2.1.1 36-1.2.1.1.1.2.2.1 38-1.2.1.1 41-1.2.1.1.2.3 42-1.2.1.1.2 43-1.2.1.1.2.2.r 44-1.2.1.1.2.2
(m / multi-sentence
:snt1 (n / note-01~e.0
:ARG1~e.1 (r2 / require-01~e.4
:ARG0 (a3 / assay-01~e.3
:mod (t4 / this~e.2))
:ARG1 (t5 / trypsinize-00
:ARG1 (c4 / cell~e.6)
:time (a4 / after~e.9
:op1 (t6 / transfect-01~e.11)
:quant (t / temporal-quantity :quant 24~e.7
:unit (h / hour~e.8))))))
:snt2 (c / cause-01~e.13
:ARG1 (p2 / possible-01~e.25
:ARG1 (i / instead-of-91~e.38
:ARG1 (s / stem-01~e.26
:ARG1 (t2 / thing~e.16
:ARG2-of~e.16 (r / result-01~e.16)
:location~e.17 (c3 / cell-line~e.24
:name (n2 / name :op1 "MDA-MB-468"~e.19,21,23)))
:ARG2~e.27 (c2 / change-01~e.29
:ARG1~e.30 (a2 / apoptosis~e.31)
:ARG1-of (d / describe-01~e.32
:ARG0~e.33 (s2 / section~e.36
:mod (p4 / previous~e.35)))))
:ARG2 (a / affect-01~e.42
:ARG0 t2
:ARG1~e.43 (p3 / proliferate-01~e.44)
:ARG1-of (t3 / true-01~e.41))))))
# ::id pmid_1684_6534.151 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To control for this , we incubated non @-@ trypsinized , siRNA @-@ transfected cells at similar confluence with BrdU to measure incorporation .
# ::alignments 1-1.5 2-1.5.2.r 3-1.5.2 5-1.1 6-1 7-1.2.2.1 7-1.2.2.1.r 11-1.2.1.1.1.1 13-1.2.1 14-1.2 15-1.3.r 16-1.3.1 17-1.3 17-1.3.1.1 18-1.3.1.1.1.r 19-1.3.1.1.1.1.1 21-1.4 22-1.4.2
(i / incubate-01~e.6
:ARG0 (w / we~e.5)
:ARG1 (c / cell~e.14
:ARG1-of (t / transfect-01~e.13
:ARG2 (n3 / nucleic-acid
:name (n / name :op1 "siRNA"~e.11)))
:ARG1-of (t2 / trypsinize-00 :polarity~e.7 -~e.7))
:ARG3~e.15 (c2 / confluence~e.17
:ARG1-of (r / resemble-01~e.16
:ARG2 (c3 / confluence~e.17
:mod~e.18 (s / small-molecule
:name (n2 / name :op1 "BrdU"~e.19)))))
:ARG4 (m / measure-01~e.21
:ARG0 w
:ARG1 (i2 / incorporate-02~e.22))
:purpose (c4 / control-01~e.1
:ARG0 w
:ARG1~e.2 (t3 / this~e.3)))
# ::id pmid_1684_6534.152 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The ' clumped ' profile of cells ( contrast to Figure 4b ) is likely a result of the acid denaturation ( recommended by the antibody manufacturer ) , as it occurs uniformly in these experiments .
# ::alignments 2-1.2.1.2.2 3-1.2.1.2.2.r 4-1.2.1.2 5-1.2.1.2.1.r 6-1.2.1.2.1 8-1.2.2 9-1.2.2.1.r 10-1.2.2.1 12-1.2.2.1.1 16-1.2 18-1.2.1 21-1.2.1.1.2 24-1.2.1.1.3 25-1.2.1.1.3.1.r 27-1.2.1.1.3.1.1.1 28-1.2.1.1.3.1 28-1.2.1.1.3.1.1 28-1.2.1.1.3.1.1.r 32-1.1.1 34-1.1 35-1.1.2.r 36-1.1.2.2 37-1.1.2 37-1.1.2.1 37-1.1.2.1.r
(c2 / cause-01
:ARG0 (u / uniform-02~e.34
:ARG1 p~e.32
:location~e.35 (t / thing~e.37
:ARG1-of~e.37 (e / experiment-01~e.37)
:mod (t2 / this~e.36)))
:ARG1 (l / likely-01~e.16
:ARG1 (r / result-01~e.18
:ARG1 (n / natural-02 :polarity -
:ARG1 (a / acid~e.21)
:ARG1-of (r2 / recommend-01~e.24
:ARG0~e.25 (t3 / thing~e.28
:ARG0-of~e.28 (m / manufacture-01~e.28
:ARG1 (a2 / antibody~e.27)))))
:ARG2 (p / profile-01~e.4
:ARG1~e.5 (c3 / cell~e.6)
:ARG1-of~e.3 (c4 / clump-02~e.2)))
:ARG1-of (c / contrast-01~e.8
:ARG2~e.9 (f / figure~e.10 :mod "4b"~e.12))))
# ::id pmid_1684_6534.153 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok BrdU incorporation ( Figure 5b ) confirms that the [ @ 3 @ H]thymidine results are not solely due to alterations in apoptosis , as 468.siMUC1 cells incorporate less BrdU than 468.siLuc ; once again , BT.siMUC1 cells show increased proliferation over BT.siLuc .
# ::alignments 0-1.2.1.1.1.1 1-1.2.1 3-1.2.1.2.1 5-1.2.1.2.1.1 8-1.2 16-1.2.2.3 18-1.2.2.1 18-1.2.2.1.r 19-1.2.2.2.2 20-1.2.2 21-1.2.2 21-1.2.2.4 21-1.2.2.4.r 22-1.2.2.2 23-1.2.2.2.1.r 24-1.2.2.2.1 26-1.2.2.4.1.r 27-1.2.2.4.1.1.1.1 28-1.2.2.4.1.1 28-1.2.2.4.1.4.1 29-1.2.2.4.1 29-1.2.2.4.1.4 30-1.2.2.4.1.3 31-1.2.2.4.1.4.2 32-1.2.2.4.1.4.r 33-1.2.2.4.1.4.1.1.1 35-1.1.3.1 36-1.1.3 38-1.1.1.1.1 39-1.1.1 39-1.1.2.1.1 40-1.1 41-1.1.2 42-1.1.2.1 44-1.1.2.1.1.1.1
(m / multi-sentence
:snt2 (s / show-01~e.40
:ARG0 (c / cell-line~e.39
:name (n / name :op1 "BT.siMUC1"~e.38))
:ARG1 (i / increase-01~e.41
:ARG1 (p / proliferate-01~e.42
:compared-to (c2 / cell-line~e.39
:name (n2 / name :op1 "BT.siLuc"~e.44))))
:mod (a / again~e.36
:mod (o / once~e.35)))
:snt1 (c3 / confirm-01~e.8
:ARG0 (i2 / incorporate-02~e.1
:ARG1 (s4 / small-molecule
:name (n3 / name :op1 "BrdU"~e.0))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.3 :mod "5b"~e.5)))
:ARG1 (c4 / cause-01~e.20,21 :polarity~e.18 -~e.18
:ARG0 (a2 / alter-01~e.22
:ARG1~e.23 (a3 / apoptosis~e.24)
:mod (s2 / sole~e.19))
:ARG1 (r / result-01~e.16
:ARG1 (s3 / small-molecule
:name (n4 / name :op1 "3H-thymidine")))
:ARG1-of~e.21 (c5 / cause-01~e.21
:ARG0~e.26 (i3 / incorporate-02~e.29
:ARG0 (c6 / cell-line~e.28
:name (n5 / name :op1 "468.siMUC1"~e.27))
:ARG1 s4
:degree (l / less~e.30)
:compared-to~e.32 (i4 / incorporate-02~e.29
:ARG0 (c7 / cell-line~e.28
:name (n6 / name :op1 "468.siLuc"~e.33))
:ARG1 s4~e.31))))))
# ::id pmid_1684_6534.154 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Given the role of MUC1 in adhesion , we examined whether MUC1 siRNA affects cellular invasion .
# ::alignments 2-1.1 3-1.1.1.r 4-1.1.1.1.1 5-1.1.2.r 6-1.1.2 8-1.2.1 9-1.2 10-1.2.2.1 10-1.2.2.1.r 11-1.1.1.1.1 12-1.2.2.2.1.1 13-1.2.2 14-1.2.2.3.1 15-1.2.2.3
(c / cause-01
:ARG0 (r / role~e.2
:poss~e.3 (p / protein
:name (n / name :op1 "MUC1"~e.4,11))
:purpose~e.5 (a / adhere-01~e.6))
:ARG1 (e / examine-01~e.9
:ARG0 (w / we~e.8)
:ARG1 (a2 / affect-01~e.13 :mode~e.10 interrogative~e.10
:ARG0 (n3 / nucleic-acid
:name (n2 / name :op1 "siRNA"~e.12)
:ARG0-of (e2 / encode-01
:ARG1 p))
:ARG1 (i / invade-01~e.15
:ARG1 (c2 / cell~e.14)))))
# ::id pmid_1684_6534.155 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In transwell assays , BT @-@ 20 cells invaded poorly , regardless of the siRNA used ( data not shown ) .
# ::alignments 1-1.2.1 2-1.2 4-1.1.1.1 6-1.1.1.1 7-1.1 8-1 9-1.3 9-1.3.r 11-1.6 14-1.6.1.1.1 15-1.6.1.2 17-1.4.1 17-1.5.1 18-1.4.1.1.1 18-1.4.1.1.1.r 18-1.5.1.1.1 18-1.5.1.1.1.r 19-1.4.1.1 19-1.5.1.1
(i / invade-01~e.8
:ARG0 (c2 / cell-line~e.7
:name (n2 / name :op1 "BT-20"~e.4,6))
:ARG1 (a / assay-01~e.2
:mod (t / transwell~e.1))
:manner~e.9 (p / poor~e.9)
:ARG1-of (d / describe-01
:ARG0 (d2 / data~e.17
:ARG1-of (s / show-01~e.19 :polarity~e.18 -~e.18)))
:ARG1-of (d3 / describe-01
:ARG0 (d4 / data~e.17
:ARG1-of (s2 / show-01~e.19 :polarity~e.18 -~e.18)))
:ARG1-of (r / regardless-91~e.11
:ARG2 (n3 / nucleic-acid
:name (n / name :op1 "siRNA"~e.14)
:ARG1-of (u / use-01~e.15))))
# ::id pmid_1684_6534.156 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok However , MDA @-@ MB @-@ 468 cells invade more readily , and were analyzed on a panel of three different extracellular matrix proteins .
# ::alignments 0-1 2-1.1.1.1.1.1 4-1.1.1.1.1.1 6-1.1.1.1.1.1 7-1.1.1.1 8-1.1.1 9-1.1.1.2.1 10-1.1.1.2 12-1.1 14-1.1.2 15-1.1.2.2.r 17-1.1.2.2 18-1.1.2.2.1.r 19-1.1.2.2.1.1 20-1.1.2.2.1.2 21-1.1.2.2.1.3.1 22-1.1.2.2.1.3 23-1.1.2.2.1
(h / have-concession-91~e.0
:ARG1 (a / and~e.12
:op1 (i / invade-01~e.8
:ARG0 (c2 / cell-line~e.7
:name (n / name :op1 "MDA-MB-468"~e.2,4,6))
:manner (r / ready-02~e.10
:degree (m / more~e.9)))
:op2 (a2 / analyze-01~e.14
:ARG1 c2
:location~e.15 (p / panel~e.17
:consist-of~e.18 (p2 / protein~e.23 :quant 3~e.19
:ARG1-of (d / differ-02~e.20)
:mod (m2 / matrix~e.22
:mod (e / extracellular~e.21)))))))
# ::id pmid_1684_6534.157 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Interestingly , 468.siMUC1 cells display somewhat decreased invasion on collagen IV , laminin , and fibronectin matrices , and on a no @-@ matrix control ( Figure 5c ) , which is in agreement with the trend towards decreased metastasis observed in Muc1 @ -/- @ × MMTV @-@ PyV MT mice [ @ 8 @ ] .
# ::alignments 0-1.3 2-1.1.1.1 3-1.1 4-1 5-1.2.4.1 6-1.2.4 7-1.2 8-1.2.2.r 9-1.2.2.1.1.1 10-1.2.2.1.1.2 12-1.2.2.2 14-1.2.2 15-1.2.2.3.1 16-1.2.2.3 18-1.2.2 21-1.2.2.4.1.1 21-1.2.2.4.1.1.r 23-1.2.2.4.1 24-1.2.2.4 26-1.2.3.1 28-1.2.3.1.1 34-1.4.r 35-1.4 36-1.4.1.r 38-1.4.1 40-1.4.1.1.1 41-1.4.1.1 42-1.4.1.1.2 43-1.4.1.1.2.1.r 44-1.4.1.1.2.1.1.1 46-1.4.1.1.2.1.2.1 49-1.4.1.1.2.2.1.2.1.1 51-1.4.1.1.2.2.1.1.1 52-1.4.1.1.2.2.1.1.2 53-1.4.1.1.2.2 56-1.4.1.1.2.3.1.1.1
(d / display-01~e.4
:ARG0 (c / cell-line~e.3
:name (n / name :op1 "468.siMUC1"~e.2))
:ARG1 (i2 / invade-01~e.7
:ARG0 c
:ARG1~e.8 (a / and~e.14,18
:op1 (p4 / protein
:name (n5 / name :op1 "collagen"~e.9 :op2 "IV"~e.10))
:op2 (l / laminin~e.12)
:op3 (m / matrix~e.16
:mod (f / fibronectin~e.15))
:op4 (c3 / control-01~e.24
:ARG1 (m2 / matrix~e.23 :polarity~e.21 -~e.21)))
:ARG1-of (d2 / describe-01
:ARG0 (f2 / figure~e.26 :mod "5c"~e.28))
:ARG1-of (d5 / decrease-01~e.6
:degree (s / somewhat~e.5)))
:ARG2-of (i / interest-01~e.0)
:ARG0-of~e.34 (a2 / agree-01~e.35
:ARG2~e.36 (t / trend-01~e.38
:ARG1 (m3 / metastasis~e.41
:ARG1-of (d3 / decrease-01~e.40)
:ARG1-of (o / observe-01~e.42
:location~e.43 (p2 / protein
:name (n2 / name :op1 "Muc1"~e.44)
:ARG2-of (m4 / mutate-01 :mod "-/-"~e.46))
:location (m5 / mouse~e.53
:mod (p3 / protein
:name (n3 / name :op1 "PyV"~e.51 :op2 "MT"~e.52)
:mod (o2 / organism
:name (n4 / name :op1 "MMTV"~e.49))))
:ARG1-of (d4 / describe-01
:ARG0 (p / publication
:ARG0-of (c4 / cite-01 :ARG1 8~e.56))))))))
# ::id pmid_1684_6534.158 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Transfection of MUC1 rescues the 468.siMUC1 phenotype
# ::alignments 1-1.1 2-1.1.1.r 3-1.1.1.1.1 4-1 6-1.2.1.1.1 7-1.2
(r / rescue-01~e.4
:ARG0 (t / transfect-01~e.1
:ARG1~e.2 (p2 / protein
:name (n / name :op1 "MUC1"~e.3)))
:ARG1 (p / phenotype~e.7
:mod (c / cell-line
:name (n2 / name :op1 "468.siMUC1"~e.6))))
# ::id pmid_1684_6534.159 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To determine if the above effects are specific to MUC1 , we created stable transfectants of the MDA @-@ MB @-@ 468 line using empty vector ( 468.Neo ) or a full @-@ length MUC1 construct ( 468.MUC1Δ8 ) that is resistant to one of the independent MUC1 @-@ directed oligonucleotides (' 882 ') .
# ::alignments 1-1.4 4-1.4.2.2.1 5-1.4.2.2 7-1.4.2 8-1.4.2.3.r 9-1.4.2.3.1.1 11-1.1 12-1 13-1.2.2 14-1.2 17-1.2.1.1.1 19-1.2.1.1.1 21-1.2.1.1.1 22-1.2.1 22-1.3.2.2.1 23-1.4.r 24-1.3.1.2 25-1.3.1 27-1.3.1.1.1 29-1.3 31-1.3.2.4.1 33-1.3.2.4 34-1.3.2.1 35-1.3.2 37-1.3.2.2.1.1.1 41-1.3.2.3 44-1.3.2.3.1.r 46-1.3.2.3.1.2.1.2 46-1.3.2.3.1.2.1.2.1 46-1.3.2.3.1.2.1.2.1.r 47-1.3.2.3.1.2.1.1.1 49-1.3.2.3.1.2.1.1 50-1.3.2.3.1 50-1.3.2.3.1.2.1 52-1.3.2.3.1.1
(c / create-01~e.12
:ARG0 (w / we~e.11)
:ARG1 (t / transfect-01~e.14
:ARG1 (c2 / cell-line~e.22
:name (n / name :op1 "MDA-MB-468"~e.17,19,21))
:ARG1-of (s2 / stable-02~e.13))
:ARG2 (o / or~e.29
:op1 (v / vector~e.25
:name (n3 / name :op1 "468.Neo"~e.27)
:ARG1-of (e / empty-02~e.24))
:op2 (c3 / construct-01~e.35
:ARG2 p2~e.34
:ARG1-of (m / mean-01
:ARG2 (c4 / cell-line~e.22
:name (n4 / name :op1 "468.MUC1Δ8"~e.37)))
:ARG0-of (r / resist-01~e.41
:ARG1~e.44 (o2 / oligonucleotide~e.50 :mod 882~e.52
:ARG1-of (i / include-91
:ARG2 (o3 / oligonucleotide~e.50
:ARG1-of (d2 / direct-01~e.49
:ARG0 p2~e.47)
:ARG0-of (d3 / depend-01~e.46 :polarity~e.46 -~e.46)))))
:ARG1-of (l / long-03~e.33
:mod (f / full~e.31))))
:purpose~e.23 (d / determine-01~e.1
:ARG0 w
:ARG1 (s / specific-02~e.7 :mode interrogative
:ARG1 (a / affect-02~e.5
:mod (a2 / above~e.4))
:ARG2~e.8 (p2 / protein
:name (n2 / name :op1 "MUC1"~e.9)))))
# ::id pmid_1684_6534.160 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok These cells were maintained in G418 @-@ containing medium to retain transgene selection .
# ::alignments 0-1.1.1 1-1.1 3-1 4-1.3.r 5-1.3.1.1.1.1 7-1.3.1 8-1.3 10-1.2 11-1.2.2.1 12-1.2.2
(m / maintain-01~e.3
:ARG1 (c / cell~e.1
:mod (t2 / this~e.0))
:purpose (r / retain-01~e.10
:ARG0 c
:ARG1 (s / select-01~e.12
:ARG1 (t / transgene~e.11)))
:location~e.4 (m2 / medium~e.8
:ARG0-of (c2 / contain-01~e.7
:ARG1 (s2 / small-molecule
:name (n / name :op1 "G418"~e.5)))))
# ::id pmid_1684_6534.161 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok As expected , 468.MUC1Δ8 cells show higher levels of both the MUC1 extracellular domain and the MUC1 @-@ CT than do 468.Neo ( Figure 6a ) .
# ::alignments 1-1.4 3-1.1.1.1 4-1.1 4-1.3 5-1 6-1.2.3 6-1.2.3.1 6-1.2.3.1.r 7-1.2.1 7-1.2.2 11-1.2.1.1.1.1 12-1.2.4.1 13-1.2.4 14-1.2 16-1.2.1.1.1.1 18-1.2.2.1.1.1 19-1.3.r 21-1.3.1.1 23-1.5.1 25-1.5.1.1
(s3 / show-01~e.5
:ARG0 (c / cell-line~e.4
:name (n2 / name :op1 "468.MUC1Δ8"~e.3))
:ARG1 (a2 / and~e.14
:op1 (l / level~e.7
:quant-of (p / protein-segment
:name (n4 / name :op1 "MUC1"~e.11,16)))
:op2 (l2 / level~e.7
:quant-of (p2 / protein-segment
:name (n3 / name :op1 "MUC1-CT"~e.18)))
:ARG1-of (h / high-02~e.6
:degree~e.6 (m / more~e.6)
:compared-to c2)
:mod (d / domain~e.13
:mod (e2 / extracellular~e.12)))
:compared-to~e.19 (c2 / cell-line~e.4
:name (n / name :op1 "468.Neo"~e.21))
:ARG1-of (e / expect-01~e.1)
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.23 :mod "6a"~e.25)))
# ::id pmid_1684_6534.162 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Note that 468.Neo have MUC1 expression comparable to parental MDA @-@ MB @-@ 468 ; the exposures in Figure 6a are lighter than those in Figure 1a , in order to clearly show the relative levels of MUC1 in the stable transfectants .
# ::alignments 0-1.1 1-1.1.1.r 2-1.1.1.2.1.1 4-1.1.1.1 5-1.1.1 6-1.1.1.3 7-1.1.1.3.1.r 8-1.1.1.3.1.2 9-1.1.1.3.1.1.1 11-1.1.1.3.1.1.1 13-1.1.1.3.1.1.1 16-1.2.1 16-1.2.3 17-1.2.1.1.r 18-1.2.1.1 20-1.2.1.1.1 23-1.2 23-1.2.2 23-1.2.2.r 24-1.2.3.r 26-1.2.3.1.r 27-1.2.3.1 29-1.2.3.1.1 32-1.2.4.r 33-1.2.4.r 34-1.2.4.r 35-1.2.4.3 36-1.2.4 38-1.2.4.2.2 39-1.2.4.2 40-1.2.4.2.1.r 41-1.2.4.2.1.1.1 42-1.2.4.4.r 44-1.2.4.4 44-1.2.4.4.1 44-1.2.4.4.1.r 45-1.2.4.4.2
(m / multi-sentence
:snt1 (n / note-01~e.0
:ARG1~e.1 (e3 / express-03~e.5
:ARG2 p2~e.4
:ARG3 (c2 / cell-line
:name (n4 / name :op1 "468.Neo"~e.2))
:ARG1-of (c5 / comparable-03~e.6
:ARG2~e.7 (c3 / cell-line
:name (n5 / name :op1 "MDA-MB-468"~e.9,11,13)
:mod (p / parent~e.8)))))
:snt2 (l / light-06~e.23
:ARG1 (e / exposure~e.16
:medium~e.17 (f / figure~e.18 :mod "6a"~e.20))
:degree~e.23 (m2 / more~e.23)
:compared-to~e.24 (e2 / expose-01~e.16
:source~e.26 (f2 / figure~e.27 :mod "1a"~e.29))
:purpose~e.32,33,34 (s / show-01~e.36
:ARG0 e
:ARG1 (l2 / level~e.39
:quant-of~e.40 (p2 / protein
:name (n2 / name :op1 "MUC1"~e.41))
:ARG1-of (r / relative-05~e.38))
:ARG1-of (c / clear-06~e.35)
:location~e.42 (c4 / cell~e.44
:ARG1-of~e.44 (s2 / stable-02~e.44)
:ARG1-of (t / transfect-01~e.45)))))
# ::id pmid_1684_6534.163 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok After MUC1 siRNA , 468.MUC1Δ8 lose some MUC1 ( likely endogenous protein , which is not siRNA @-@ resistant ) but retain high @-@ level expression , while 468.Neo show a decrease in MUC1 levels similar to parental 468.siMUC1 cells ( Figures 6a , b ) .
# ::alignments 0-1.1.1.4 1-1.1.1.2.1.1 2-1.1.1.4.1.1.1 4-1.1.1.1.1.1 5-1.1.1 6-1.1.1.2.2 7-1.1.1.2.1.1 9-1.1.1.2.3.1 10-1.1.1.2.3.1.1.1 11-1.1.1.2.3.1.1 15-1.1.1.2.3.1.1.2.1 15-1.1.1.2.3.1.1.2.1.r 16-1.1.1.2.3.1.1.2.2 18-1.1.1.2.3.1.1.2 20-1.1 21-1.1.1.3 22-1.1.1.3.3 24-1.2.2.1 25-1.1.1.3.2 27-1 27-1.1.1.4.r 28-1.2.1.1.1 29-1.2 31-1.2.2 33-1.2.2.1.1 34-1.2.2.1 35-1.2.2.2 37-1.2.2.2.1.2 38-1.2.2.2.1.1.1 39-1.1.1.1 39-1.2.1 39-1.2.2.2.1 41-1.3.1.1 41-1.3.1.2 43-1.3.1.1.1
(c / contrast-01~e.27
:ARG1 (c5 / contrast-01~e.20
:ARG1 (l / lose-02~e.5
:ARG0 (c2 / cell-line~e.39
:name (n2 / name :op1 "468.MUC1Δ8"~e.4))
:ARG1 (p3 / protein
:name (n3 / name :op1 "MUC1"~e.1,7)
:mod (s2 / some~e.6)
:ARG1-of (m / mean-01
:ARG2 (l3 / likely-01~e.9
:ARG1 (p2 / protein~e.11
:mod (m2 / monocot~e.10)
:ARG0-of (r / resist-01~e.18 :polarity~e.15 -~e.15
:ARG1 n6~e.16)))))
:ARG2 (r3 / retain-01~e.21
:ARG0 c2
:ARG1 (e / express-03~e.25)
:ARG1-of (h / high-02~e.22))
:time~e.27 (a / after~e.0
:op1 (n6 / nucleic-acid
:name (n / name :op1 "siRNA"~e.2)
:ARG0-of (e2 / encode-01
:ARG1 p3)))))
:ARG2 (s / show-01~e.29
:ARG0 (c3 / cell-line~e.39
:name (n4 / name :op1 "468.Neo"~e.28))
:ARG1 (d / decrease-01~e.31
:ARG1 (l2 / level~e.24,34
:quant-of p3~e.33)
:ARG1-of (r4 / resemble-01~e.35
:ARG2 (c4 / cell-line~e.39
:name (n5 / name :op1 "468.siMUC1"~e.38)
:mod (p / parent~e.37)))))
:ARG1-of (d2 / describe-01
:ARG0 (a2 / and
:op1 (f / figure~e.41 :mod "6a"~e.43)
:op2 (f2 / figure~e.41 :mod "6b"))))
# ::id pmid_1684_6534.164 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The difference in the amount of MUC1 knockdown between 468.Neo and 468.MUC1Δ8 is highlighted by the purple shading in Figure 6b @ .
# ::alignments 1-1.2 2-1.2.1.r 4-1.2.1 5-1.2.4.r 6-1.2.4.1.1.1 7-1.2.4 9-1.2.2.1.1 11-1.2.3.1.1 13-1 14-1.1.r 16-1.1.1 17-1.1 18-1.3.r 19-1.3 21-1.3.1
(h / highlight-01~e.13
:ARG0~e.14 (s / shade-01~e.17
:ARG0 (p / purple~e.16))
:ARG1 (d / differ-02~e.1
:ARG1~e.2 (a / amount-01~e.4)
:ARG1 (c / cell-line
:name (n2 / name :op1 "468.Neo"~e.9))
:ARG2 (c2 / cell-line
:name (n3 / name :op1 "468.MUC1Δ8"~e.11))
:ARG3~e.5 (k / knock-down-02~e.7
:ARG1 (p2 / protein
:name (n / name :op1 "MUC1"~e.6))))
:medium~e.18 (f / figure~e.19 :mod "6b"~e.21))
# ::id pmid_1684_6534.165 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok BrdU incorporation ( Figure 6c ) indicates that 468.Neo show decreased nucleotide incorporation after MUC1 siRNA compared to control ( 3.3 % versus 25.0 % , respectively ) ; this is not seen in 468.MUC1Δ8 cells , which show similar levels of BrdU incorporation regardless of the siRNA used ( 21.5 % for luciferase , 23.9 % for MUC1 ) .
# ::alignments 0-1.1.1.1.1.1 1-1.1.2.2 3-1.1.3.1 5-1.1.3.1.1 8-1.1 10-1.1.2.1.1.1 11-1.1.2 12-1.1.2.2.2 13-1.1.2.2.1 14-1.1.1 14-1.1.2.2 15-1.1.2.3 16-1.1.2.3.1.2.1.1.1 17-1.1.2.3.1.1.1 18-1.1.2.2.2.1.r 20-1.1.2.2.2.1 22-1.1.2.2.2.1.1.1.1.1 23-1.1.2.2.2.1.1.1.1 23-1.1.2.2.2.1.1.1.2 24-1.1.2.2.2.1.1.1 25-1.1.2.2.2.1.1.1.2.1 26-1.1.2.2.2.1.1.1.2 31-1.2.2 33-1.2.1 33-1.2.1.r 34-1.2 35-1.2.3.r 36-1.2.3.1.1 37-1.1.2.1 37-1.2.3 40-1.2.3.2 41-1.2.3.2.1.1 42-1.2.3.2.1 43-1.2.3.2.1.2.r 44-1.2.3.2.1.2.1.1.1 45-1.2.3.2.1.2 46-1.2.3.2.2 49-1.2.3.2.2.1.1.1 50-1.2.3.2.2.1.2 52-1.2.3.2.2.1.3.1.1.1 53-1.2.3.2.2.1.3.1.1 54-1.2.3.2.2.1.3.1.1.2.r 55-1.2.3.2.2.1.3.1.1.2 57-1.2.3.2.2.1.3.1.2.1 58-1.2.3.2.2.1.3.1.2 59-1.2.3.2.2.1.3.1.1.2.r 59-1.2.3.2.2.1.3.1.2.2.r 60-1.2.3.2.2.1.3.1.2.2.1.1
(m / multi-sentence
:snt1 (i / indicate-01~e.8
:ARG0 (i3 / incorporate-02~e.14
:ARG1 (s5 / small-molecule
:name (n4 / name :op1 "BrdU"~e.0)))
:ARG1 (s3 / show-01~e.11
:ARG0 (c2 / cell-line~e.37
:name (n5 / name :op1 "468.Neo"~e.10))
:ARG1 (i4 / incorporate-02~e.1,14
:ARG1 (n6 / nucleotide~e.13)
:ARG1-of (d / decrease-01~e.12
:compared-to~e.18 (c3 / control~e.20
:ARG1-of (m2 / mean-01
:ARG2 (v / versus~e.24
:op1 (p / percentage-entity~e.23 :value 3.3~e.22)
:op2 (p2 / percentage-entity~e.23,26 :value 25.0~e.25))))))
:time (a / after~e.15
:op1 (n10 / nucleic-acid
:name (n7 / name :op1 "siRNA"~e.17)
:ARG0-of (e / encode-01
:ARG1 (p7 / protein
:name (n8 / name :op1 "MUC1"~e.16))))))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.3 :mod "6c"~e.5)))
:snt2 (s / see-01~e.34 :polarity~e.33 -~e.33
:ARG1 (t / this~e.31)
:location~e.35 (c / cell-line~e.37
:name (n / name :op1 "468.MUC1Δ8"~e.36)
:ARG0-of (s2 / show-01~e.40
:ARG1 (l / level~e.42
:ARG1-of (r2 / resemble-01~e.41)
:degree-of~e.43 (i2 / incorporate-02~e.45
:ARG1 (s4 / small-molecule
:name (n2 / name :op1 "BrdU"~e.44))))
:ARG1-of (r / regardless-91~e.46
:ARG2 (n11 / nucleic-acid
:name (n3 / name :op1 "siRNA"~e.49)
:ARG1-of (u / use-01~e.50)
:ARG1-of (m3 / mean-01
:ARG2 (a2 / and
:op1 (p3 / percentage-entity~e.53 :value 21.5~e.52
:prep-for~e.54,59 (l2 / luciferase~e.55))
:op2 (p4 / percentage-entity~e.58 :value 23.9~e.57
:quant-of~e.59 (p8 / protein
:name (n9 / name :op1 "MUC1"~e.60)))))))))))
# ::id pmid_1684_6534.166 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok 468.Neo cells display a more dramatic decrease in BrdU incorporation after MUC1 siRNA than what is seen in parental 468.siMUC1 cells , which may reflect the additional stress of being maintained in G418 @-@ containing medium .
# ::alignments 0-1.1.1.1 1-1.1 2-1 4-1.2.2.1 5-1.2.2 6-1.2 7-1.2.1.r 8-1.2.1.1.1.1 9-1.2.1 10-1.3 11-1.3.1.2.1.1.1 12-1.3.1.1.1 13-1.2.3.r 14-1.2.3 16-1.2.3.1 17-1.2.3.1.1.r 18-1.2.3.1.1.2 19-1.2.3.1.1.1.1 20-1.2.3.1.1 23-1.2.3.2.2 24-1.2.3.2 26-1.2.3.2.1.2 27-1.2.3.2.1 30-1.2.3.2.1.1 31-1.2.3.2.1.1.1.r 32-1.2.3.2.1.1.1.1.1.1.1 34-1.2.3.2.1.1.1.1 35-1.2.3.2.1.1.1
(d / display-01~e.2
:ARG0 (c / cell-line~e.1
:name (n5 / name :op1 "468.Neo"~e.0))
:ARG1 (d2 / decrease-01~e.6
:ARG1~e.7 (i / incorporate-02~e.9
:ARG1 (s3 / small-molecule
:name (n / name :op1 "BrdU"~e.8)))
:ARG2 (d3 / dramatic~e.5
:degree (m / more~e.4))
:compared-to~e.13 (t / thing~e.14
:ARG1-of (s / see-01~e.16
:location~e.17 (c2 / cell-line~e.20
:name (n4 / name :op1 "468.siMUC1"~e.19)
:mod (p2 / parent~e.18)))
:ARG1-of (r2 / reflect-01~e.24
:ARG2 (s2 / stress-01~e.27
:ARG0 (m2 / maintain-01~e.30
:location~e.31 (m3 / medium~e.35
:ARG0-of (c3 / contain-01~e.34
:ARG1 (s4 / small-molecule
:name (n6 / name :op1 "G418"~e.32)))))
:mod (a2 / additional~e.26))
:ARG1-of (p / possible-01~e.23))))
:time (a / after~e.10
:op1 (n7 / nucleic-acid
:name (n2 / name :op1 "siRNA"~e.12)
:ARG0-of (e / encode-01
:ARG1 (p4 / protein
:name (n3 / name :op1 "MUC1"~e.11))))))
# ::id pmid_1684_6534.167 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Similarly , analysis of apoptosis in trypsinized cells indicates that the increased apoptosis seen in parental 468.siMUC1 cells is also present in the 468.Neo line after MUC1 siRNA ( Figure 6d ; 43.6 % in control versus 59.6 % in MUC1 siRNA ) .
# ::alignments 0-1.3 2-1.1 3-1.1.1.r 4-1.1.1 7-1.2.1.1.1 8-1 11-1.2.1.2 12-1.2.1 13-1.2.1.1 14-1.2.1.1.1.2.r 15-1.2.1.1.1.2 16-1.2.1.1.1.1.1 17-1.1.1.1.1 19-1.2.3 20-1.1.1.1 20-1.2 21-1.2.2.r 23-1.2.2.1.1 24-1.2.2 25-1.2.4 26-1.2.4.1 27-1.2.4.1 29-1.4.1 31-1.4.1.1 34-1.2.6.1.1 35-1.2.6.1 35-1.2.6.1.2 35-1.2.6.1.2.r 36-1.2.5.r 37-1.2.5 39-1.2.6.1.2.1 40-1.2.6.1.2 41-1.2.5.1.r 42-1.2.5.1.2.1.1.1 43-1.2.5.1.1.1
(i / indicate-01~e.8
:ARG0 (a / analyze-01~e.2
:ARG1~e.3 (a2 / apoptosis~e.4
:ARG1-of (p5 / present-02~e.20
:ARG2 (c / cell~e.17
:ARG1-of (t / trypsinize-00)))))
:ARG1 (p6 / present-02~e.20
:ARG1 (a3 / apoptosis~e.12
:ARG1-of (s / see-01~e.13
:location (c2 / cell-line~e.7
:name (n / name :op1 "468.siMUC1"~e.16)
:mod~e.14 (p3 / parent~e.15)))
:ARG1-of (i2 / increase-01~e.11))
:ARG2~e.21 (c3 / cell-line~e.24
:name (n2 / name :op1 "468.Neo"~e.23))
:mod (a4 / also~e.19)
:time (a5 / after~e.25
:op1 n5~e.26,27)
:mod~e.36 (c4 / control-01~e.37
:location~e.41 (n5 / nucleic-acid
:name (n3 / name :op1 "siRNA"~e.43)
:ARG0-of (e / encode-01
:ARG1 (p4 / protein
:name (n4 / name :op1 "MUC1"~e.42)))))
:ARG1-of (m / mean-01
:ARG2 (p / percentage-entity~e.35 :value 43.6~e.34
:compared-to~e.35 (p2 / percentage-entity~e.35,40 :value 59.6~e.39))))
:ARG1-of (r / resemble-01~e.0)
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.29 :mod "6d"~e.31)))
# ::id pmid_1684_6534.168 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok However , in 468.MUC1Δ8 cells , the level of apoptosis after luciferase siRNA ( 34.1 %) is lower than that in 468.Neo cells ; MUC1 siRNA increases the amount of apoptosis slightly ( 42.8 %) , restoring it to a level similar to that seen in luciferase siRNA @-@ treated 468.Neo cells .
# ::alignments 0-1.1 3-1.1.1.1.2.1.1 4-1.1.1.1.2 4-1.1.1.3.2 7-1.1.1.1 7-1.1.1.3 8-1.1.1.1.1.r 9-1.1.1.1.1 10-1.1.1.2 11-1.1.1.2.1.2.1 12-1.1.1.2.1.1.1 14-1.1.1.1.3.1.1 17-1.1.1 17-1.1.1.4 17-1.1.1.4.r 18-1.1.1.3.r 21-1.1.1.3.2.1.1 22-1.1.1.1.2 24-1.2.1.2.1.1.1 25-1.2.1.1.1 26-1.2 28-1.2.2 29-1.2.2.1.r 30-1.2.2.1 31-1.2.3 33-1.2.2.2.1.1 36-1.2.4 37-1.2.4.1 38-1.2.4.2.r 40-1.2.4.2 40-1.2.4.2.1.1 41-1.2.4.2.1 44-1.2.4.2.1.1.1 45-1.2.4.2.1.1.1.1.r 46-1.2.4.2.1.1.1.1.2.1.2.1 47-1.2.4.2.1.1.1.1.2.1.1.1 49-1.2.4.2.1.1.1.1.2 50-1.2.4.2.1.1.1.1.1.1 51-1.2.4.2.1.1.1.1
(m2 / multi-sentence
:snt1 (h / have-concession-91~e.0
:ARG1 (l2 / low-04~e.17
:ARG1 (l3 / level~e.7
:quant-of~e.8 (a / apoptosis~e.9)
:location (c2 / cell-line~e.4,22
:name (n2 / name :op1 "468.MUC1Δ8"~e.3))
:ARG1-of (m3 / mean-01
:ARG2 (p / percentage-entity :value 34.1~e.14)))
:time (a2 / after~e.10
:op1 (n8 / nucleic-acid
:name (n / name :op1 "siRNA"~e.12)
:ARG0-of (e / encode-01
:ARG1 (l4 / luciferase~e.11))))
:compared-to~e.18 (l5 / level~e.7
:quant-of a
:location (c4 / cell-line~e.4
:name (n3 / name :op1 "468.Neo"~e.21)))
:degree~e.17 (m / more~e.17)))
:snt2 (i / increase-01~e.26
:ARG0 (n9 / nucleic-acid
:name (n5 / name :op1 "siRNA"~e.25)
:ARG0-of (e2 / encode-01
:ARG1 (p3 / protein
:name (n4 / name :op1 "MUC1"~e.24))))
:ARG1 (a3 / amount~e.28
:quant-of~e.29 (a4 / apoptosis~e.30)
:ARG1-of (m4 / mean-01
:ARG2 (p2 / percentage-entity :value 42.8~e.33)))
:ARG2 (s / slight~e.31)
:ARG0-of (r / restore-02~e.36
:ARG1 a3~e.37
:ARG2~e.38 (l / level~e.40
:ARG1-of (r4 / resemble-01~e.41
:ARG2 (l6 / level~e.40
:ARG1-of (s2 / see-01~e.44
:location~e.45 (c3 / cell-line~e.51
:name (n6 / name :op1 "468.Neo"~e.50)
:ARG1-of (t / treat-04~e.49
:ARG2 (n10 / nucleic-acid
:name (n7 / name :op1 "siRNA"~e.47)
:ARG0-of (e3 / encode-01
:ARG1 (l7 / luciferase~e.46))))))))))))
# ::id pmid_1684_6534.169 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Together , these studies suggest that the above @-@ described results are specific to MUC1 , as stable transfection of an siRNA @-@ resistant MUC1 rescues the phenotype seen in 468.siMUC1 cells .
# ::alignments 0-1.1.1 2-1.1.2 3-1.1 4-1 5-1.2.r 7-1.2.2.1.2.1 9-1.2.2.1.2 10-1.2.2.1 10-1.2.2.1.1 10-1.2.2.1.1.r 12-1.2.2 13-1.2 13-1.2.2.2.r 14-1.2.2.2.1.1 16-1.2.1.r 17-1.2.1.1.2 18-1.2.1.1 19-1.2.1.1.1.r 21-1.2.1.1.1.2.1.1.1 23-1.2.1.1.1 23-1.2.1.1.1.2 23-1.2.1.1.1.2.r 24-1.2.1.1.1.1.1 25-1.2.1 27-1.2.1.2 28-1.2.1.2.1 29-1.2.1.2.1.1.r 30-1.2.1.2.1.1.1.1 31-1.2.1.2.1.1
(s / suggest-01~e.4
:ARG0 (s7 / study-01~e.3
:mod (t3 / together~e.0)
:mod (t / this~e.2))
:ARG1~e.5 (c / cause-01~e.13
:ARG0~e.16 (r / rescue-01~e.25
:ARG0 (t4 / transfect-01~e.18
:ARG2~e.19 (p3 / protein~e.23
:name (n2 / name :op1 "MUC1"~e.24)
:ARG0-of~e.23 (r2 / resist-01~e.23
:ARG1 (n5 / nucleic-acid
:name (n3 / name :op1 "siRNA"~e.21))))
:ARG1-of (s6 / stable-03~e.17))
:ARG1 (p / phenotype~e.27
:ARG1-of (s5 / see-01~e.28
:location~e.29 (c2 / cell-line~e.31
:name (n4 / name :op1 "468.siMUC1"~e.30)))))
:ARG1 (s3 / specific-02~e.12
:ARG1 (t2 / thing~e.10
:ARG2-of~e.10 (r4 / result-01~e.10)
:ARG1-of (d / describe-01~e.9
:location (a / above~e.7)))
:ARG2~e.13 (p2 / protein
:name (n / name :op1 "MUC1"~e.14)))))
# ::id pmid_1901_8267.1 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok KRAS or BRAF mutation status is a useful predictor of sensitivity to MEK inhibition in ovarian cancer ( PMID : 19018267 )
# ::alignments 1-1.1.1.1.1.1.1 3-1.1 5-1.1.2.1.1.1.1 7-1.1.1.1 7-1.1.2.1 8-1.1.1 8-1.1.2 11-1 14-1.2.2 15-1.2.2.1.r 16-1.2.2.1.1.1.1 17-1.2.2.1 18-1.2.2.1.2.r 19-1.2.2.1.2.2.1 20-1.2.2.1.2.2.2
(u / useful-05~e.11
:ARG1 (o / or~e.3
:op1 (s / status~e.8
:mod (m / mutate-01~e.7
:ARG1 (g2 / gene
:name (n4 / name :op1 "KRAS"~e.1))))
:op2 (s2 / status~e.8
:mod (m2 / mutate-01~e.7
:ARG1 (g / gene
:name (n3 / name :op1 "BRAF"~e.5)))))
:ARG2 (p / predict-01
:ARG0 o
:ARG1 (s3 / sensitive-03~e.14
:ARG1~e.15 (i / inhibit-01~e.17
:ARG1 (e / enzyme
:name (n / name :op1 "MEK"~e.16))
:location~e.18 (d / disease :wiki "Ovarian_cancer"
:name (n2 / name :op1 "ovarian"~e.19 :op2 "cancer"~e.20)))))
:ARG1-of (d2 / describe-01
:ARG0 (p2 / publication-91 :ARG8 "PMID19018267")))
# ::id pmid_1901_8267.119 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Results
# ::alignments 1-1 1-1.1 1-1.1.r
(t / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1))
# ::id pmid_1901_8267.120 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Identification of KRAS and BRAF mutations
# ::alignments 1-1 4-1.1.1.1.1.1 6-1.1 8-1.1.2.1.1.1 10-1.1.1 10-1.1.2
(i / identify-01~e.1
:ARG1 (a2 / and~e.6
:op1 (m2 / mutate-01~e.10
:ARG1 (g / gene
:name (n / name :op1 "KRAS"~e.4)))
:op2 (m / mutate-01~e.10
:ARG1 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.8)))))
# ::id pmid_1901_8267.121 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The mutational status of KRAS and BRAF in all 45 ovarian carcinomas is summarised in Table 1 @ .
# ::alignments 1-1.1.1 2-1.1 5-1.1.2.1.1.1 7-1.1.2 9-1.1.2.2.1.1 11-1.1.3.r 12-1.1.3.3 13-1.1.3.1 14-1.1.3.2 15-1.1.3 20-1.2 21-1.2.1
(s / summarize-01
:ARG1 (s2 / status~e.2
:mod (m / mutate-01~e.1)
:poss (a / and~e.7
:op1 (g / gene
:name (n / name :op1 "KRAS"~e.5))
:op2 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.9)))
:location~e.11 (c / carcinoma~e.15 :quant 45~e.13
:mod (o / ovary~e.14)
:mod (a2 / all~e.12)))
:location (t / table~e.20 :mod 1~e.21))
# ::id pmid_1901_8267.122 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Somatic mutations of KRAS were identified in 8 ( 13.7 %) out of 58 ovarian carcinomas .
# ::alignments 0-1.1.2 1-1.1 4-1.1.1.1.1 7-1 8-1.2.r 9-1.2.1 11-1.2.2.2.1 15-1.2.2.1.1 16-1.2.2.1.2 17-1.2 17-1.2.2.1
(i / identify-01~e.7
:ARG1 (m / mutate-01~e.1
:ARG1 (g / gene
:name (n / name :op1 "KRAS"~e.4))
:mod (s / somatic~e.0))
:location~e.8 (c / carcinoma~e.17 :quant 8~e.9
:ARG1-of (i2 / include-91
:ARG2 (c2 / carcinoma~e.17 :quant 58~e.15
:mod (o / ovary~e.16))
:ARG3 (p / percentage-entity :value 13.7~e.11))))
# ::id pmid_1901_8267.123 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In contrast , somatic mutations of BRAF were identified in 5 ( 8.6 %) out of 58 ovarian carcinomas .
# ::alignments 1-1 3-1.1.1.2 4-1.1.1 7-1.1.1.1.1.1 10-1.1 11-1.1.2.r 12-1.1.2.1 14-1.1.2.2.2.1 18-1.1.2.2.1.1 19-1.1.2.2.1.2 20-1.1.2 20-1.1.2.2.1
(c / contrast-01~e.1
:ARG2 (i / identify-01~e.10
:ARG1 (m / mutate-01~e.4
:ARG1 (g / gene
:name (n / name :op1 "BRAF"~e.7))
:mod (s / somatic~e.3))
:location~e.11 (c2 / carcinoma~e.20 :quant 5~e.12
:ARG1-of (i2 / include-91
:ARG2 (c3 / carcinoma~e.20 :quant 58~e.18
:mod (o / ovary~e.19))
:ARG3 (p / percentage-entity :value 8.6~e.14)))))
# ::id pmid_1901_8267.124 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Somatic mutations of either KRAS or BRAF were identified in 12 ( 20.6 %) out of 58 ovarian carcinomas .
# ::alignments 0-1.1.2 1-1.1 5-1.1.1.1.1.1 7-1.1.1 9-1.1.1.2.1.1 12-1 13-1.2.r 14-1.2.1 16-1.2.2.2.1 20-1.2.2.1.1 21-1.2.2.1.2 22-1.2 22-1.2.2.1
(i / identify-01~e.12
:ARG1 (m / mutate-01~e.1
:ARG1 (o / or~e.7
:op1 (g / gene
:name (n / name :op1 "KRAS"~e.5))
:op2 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.9)))
:mod (s / somatic~e.0))
:location~e.13 (c / carcinoma~e.22 :quant 12~e.14
:ARG1-of (i2 / include-91
:ARG2 (c2 / carcinoma~e.22 :quant 58~e.20
:mod (o2 / ovary~e.21))
:ARG3 (p / percentage-entity :value 20.6~e.16))))
# ::id pmid_1901_8267.125 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Most KRAS mutations were located at codon 12 and all BRAF mutations at codon 600 .
# ::alignments 0-1.1.1.2 2-1.1.1.1.1.1 4-1.1.1 5-1.1 6-1.1 7-1.1 8-1.1.2 9-1.1.2.1 10-1 11-1.2.1.2 13-1.2.1.1.1.1 15-1.2.1 16-1.2 17-1.2.2 18-1.2.2.1
(a / and~e.10
:op1 (b / be-located-at-91~e.5,6,7
:ARG1 (m / mutate-01~e.4
:ARG1 (g / gene
:name (n / name :op1 "KRAS"~e.2))
:mod (m2 / most~e.0))
:ARG2 (c / codon~e.8 :mod 12~e.9))
:op2 (b2 / be-located-at-91~e.16
:ARG1 (m3 / mutate-01~e.15
:ARG1 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.13))
:mod (a2 / all~e.11))
:ARG2 (c2 / codon~e.17 :mod 600~e.18)))
# ::id pmid_1901_8267.126 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Both of these codons are mutation hot spots .
# ::alignments 0-1.3.2 2-1.3.1 3-1.3 4-1.3.r 5-1.2 6-1.1 7-1
(s / spot~e.7
:ARG1-of (h / hot-03~e.6)
:location-of (m / mutate-01~e.5)
:domain~e.4 (c / codon~e.3
:mod (t / this~e.2)
:mod (b / both~e.0)))
# ::id pmid_1901_8267.127 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Interestingly , simultaneous mutations of KRAS and BRAF did not occur in the tested ovarian carcinomas with the exception of one mucinous case .
# ::alignments 0-1.5 2-1.2.3 3-1.2.1 3-1.2.2 6-1.2.1.1.1.1 8-1.2 10-1.2.2.1.1.1 13-1.1 13-1.1.r 17-1.3.1 18-1.3.2 19-1.3 22-1.4 25-1.4.1.1 26-1.4.1
(b / be-located-at-91 :polarity~e.13 -~e.13
:ARG1 (a / and~e.8
:op1 (m / mutate-01~e.3
:ARG1 (g / gene
:name (n / name :op1 "KRAS"~e.6)))
:op2 (m2 / mutate-01~e.3
:ARG1 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.10)))
:mod (s / simultaneous~e.2))
:ARG2 (c / carcinoma~e.19
:ARG1-of (t / test-01~e.17)
:mod (o / ovary~e.18))
:ARG2-of (e / except-01~e.22
:ARG1 (c2 / case-04~e.26
:ARG1 (m3 / mucin~e.25)))
:ARG2-of (i / interest-01~e.0))
# ::id pmid_1901_8267.128 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok A panel of ovarian cancer cell lines and primary cultures was first analysed for tumour mutation status in the KRAS and BRAF genes .
# ::alignments 1-1.1 2-1.1.1.r 3-1.1.1.1.1.2.1 4-1.1.1.1.1.2.2 5-1.1.1.1 6-1.1.1.1 7-1.1.1 8-1.1.1.2.2 9-1.1.1.2 9-1.1.1.2.1 9-1.1.1.2.1.r 11-1.2 12-1 13-1.3.r 14-1.3.1.1 15-1.3.1 16-1.3 20-1.3.2.1.1.1 22-1.3.2 24-1.3.2.2.1.1 26-1.3.2.1 26-1.3.2.2
(a / analyze-01~e.12
:ARG1 (p / panel~e.1
:consist-of~e.2 (a2 / and~e.7
:op1 (c / cell-line~e.5,6
:mod (d / disease :wiki "Ovarian_cancer"
:name (n / name :op1 "ovarian"~e.3 :op2 "cancer"~e.4)))
:op2 (t2 / thing~e.9
:ARG1-of~e.9 (c3 / culture-01~e.9)
:mod (p2 / primary~e.8))))
:time (f / first~e.11)
:purpose~e.13 (s / status~e.16
:mod (m / mutate-01~e.15
:ARG1 (t / tumor~e.14))
:location (a3 / and~e.22
:op1 (g / gene~e.26
:name (n2 / name :op1 "KRAS"~e.20))
:op2 (g2 / gene~e.26
:name (n3 / name :op1 "BRAF"~e.24)))))
# ::id pmid_1901_8267.129 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok As shown in Figure 1 , three ovarian cancer cell lines harboured either KRAS or BRAF mutations .
# ::alignments 1-1.3 4-1.3.1 5-1.3.1.1 8-1.1.1 9-1.1.2.2.1 10-1.1.2.2.2 11-1.1 12-1.1 13-1 16-1.2.1.1.1.1 18-1.2 20-1.2.2.1.1.1 22-1.2.1 22-1.2.2
(h / harbor-01~e.13
:ARG0 (c / cell-line~e.11,12 :quant 3~e.8
:mod (d / disease :wiki "Ovarian_cancer"
:name (n / name :op1 "ovarian"~e.9 :op2 "cancer"~e.10)))
:ARG1 (o2 / or~e.18
:op1 (m / mutate-01~e.22
:ARG1 (g / gene
:name (n2 / name :op1 "KRAS"~e.16)))
:op2 (m2 / mutate-01~e.22
:ARG1 (g2 / gene
:name (n3 / name :op1 "BRAF"~e.20))))
:ARG1-of (s / show-01~e.1
:ARG0 (f / figure~e.4 :mod 1~e.5)))
# ::id pmid_1901_8267.130 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The frequency of either KRAS or BRAF mutations in conventional serous high @-@ grade carcinomas ( 4.0 % : 1 @/@ 25 ) was significantly lower than in the other histological type ( 32.2 % : 10 @/@ 31 ) .
# ::alignments 1-1.1.1 1-1.1.2 5-1.1.1.1.1.1.1 7-1.1 9-1.1.2.1.1.1.1 11-1.1.1.1 11-1.1.2.1 13-1.1.3.2.1.3.1 14-1.1.3.2.1.3 15-1.1.3.2.1.2.1 17-1.1.3.2.1.2 18-1.1.3 18-1.1.3.2.1 21-1.1.3.2.2 23-1.1.3.1 25-1.1.3.2.1.1 29-1 29-1.2 29-1.2.r 30-1.1.4.r 33-1.1.4.2.1.3 34-1.1.4.2.1.2 35-1.1.4 35-1.1.4.2.1 37-1.1.4.2.2.1 38-1.1.4.2.2 40-1.1.4.1 42-1.1.4.2.1.1
(l2 / low-04~e.29
:ARG1 (o3 / or~e.7
:op1 (h3 / have-frequency-91~e.1
:ARG1 (m2 / mutate-01~e.11
:ARG1 (g / gene
:name (n / name :op1 "KRAS"~e.5))))
:op2 (h4 / have-frequency-91~e.1
:ARG1 (m3 / mutate-01~e.11
:ARG1 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.9))))
:location (c / carcinoma~e.18 :quant 1~e.23
:ARG1-of (i / include-91
:ARG2 (c3 / carcinoma~e.18 :quant 25~e.25
:mod (g3 / grade~e.17
:ARG1-of (h / high-02~e.15))
:mod (s / serum~e.14
:mod (c2 / conventional~e.13)))
:ARG3 (p / percentage-entity~e.21 :value 4)))
:compared-to~e.30 (t / type~e.35 :quant 10~e.40
:ARG1-of (i2 / include-91
:ARG2 (t2 / type~e.35 :quant 31~e.42
:mod (h2 / histology~e.34)
:mod (o2 / other~e.33))
:ARG3 (p2 / percentage-entity~e.38 :value 32.2~e.37))))
:degree~e.29 (m / more~e.29))
# ::id pmid_1901_8267.131 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Relationship between KRAS @/@ BRAF mutations and p @-@ ERK1 @/@ 2 expression or clinicopathological factors
# ::alignments 1-1 4-1.1.1.1.1.1 5-1.1.1 6-1.1.1.2.1.1 8-1.1 10-1.2.1.1.2 12-1.2.1.1.1.1 13-1.1.1 14-1.2.1.1.1.1 15-1.2.1 16-1.2 18-1.2.2
(r / relation-03~e.1
:ARG0 (m / mutate-01~e.8
:ARG1 (s / slash~e.5,13
:op1 (g / gene
:name (n / name :op1 "KRAS"~e.4))
:op2 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.6))))
:ARG2 (o / or~e.16
:op1 (e / express-03~e.15
:ARG2 (e2 / enzyme
:name (n3 / name :op1 "ERK1/2"~e.12,14)
:ARG3-of (p / phosphorylate-01~e.10)))
:op2 (f / factor~e.18
:mod (c / clinicopathologic))))
# ::id pmid_1901_8267.132 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The immunoreactivity of active p @-@ ERK1 @/@ 2 was detected in both the nucleus and the cytoplasm of the tumour cells ( Figure 2 ) .
# ::alignments 4-1.1.1.2 6-1.1.1.1.1 8-1.1.1.1.1 8-1.3.1.1 10-1 14-1.2.1 15-1.2 17-1.2.2 18-1.2.1.1.r 20-1.2.1.1.1 21-1.2.1.1 24-1.3.1 25-1.1.1.1.1 25-1.3.1.1
(d / detect-01~e.10
:ARG1 (i / immunoreact-00
:ARG1 (e / enzyme
:name (n / name :op1 "ERK1/2"~e.6,8,25)
:ARG3-of (p / phosphorylate-01~e.4)
:ARG1-of (a / activate-01)))
:location (a2 / and~e.15
:op1 (n2 / nucleus~e.14
:part-of~e.18 (c / cell~e.21
:mod (t / tumor~e.20)))
:op2 (c2 / cytoplasm~e.17
:part-of c))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.24 :mod 2~e.8,25)))
# ::id pmid_1901_8267.133 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok This is consistent with an earlier report ( Mizumoto et al , 2007 ) .
# ::alignments 0-1.1 2-1 3-1.2.r 5-1.2.1 5-1.2.1.1 5-1.2.1.1.r 6-1.2 9-1.3.1.1.1.1.1 11-1.3.1.1 12-1.3.1.1.2.1 15-1.3.1.2.1
(c / consistent-01~e.2
:ARG1 (t / this~e.0)
:ARG2~e.3 (r / report-01~e.6
:time (e2 / early~e.5
:degree~e.5 (m / more~e.5)))
:ARG1-of (d / describe-01
:ARG0 (p / publication-91
:ARG0 (a / and~e.11
:op1 (p2 / person
:name (n / name :op1 "Mizumoto"~e.9))
:op2 (p3 / person
:mod (o / other~e.12)))
:time (d2 / date-entity :year 2007~e.15))))
# ::id pmid_1901_8267.134 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Positive active p @-@ ERK1 @/@ 2 was identified in 27 ( 46.6 %) out of 58 ovarian carcinomas .
# ::alignments 0-1.1.4 2-1.1.2 4-1.1.1.1 6-1.1.1.1 8-1 9-1.2.r 10-1.2.1 12-1.2.2.2.1 16-1.2.2.1.1 17-1.2.2.1.2 18-1.2 18-1.2.2.1
(i / identify-01~e.8
:ARG1 (e / enzyme
:name (n / name :op1 "ERK1/2"~e.4,6)
:ARG3-of (p / phosphorylate-01~e.2)
:ARG1-of (a / activate-01)
:mod (p2 / positive~e.0))
:location~e.9 (c / carcinoma~e.18 :quant 27~e.10
:ARG1-of (i2 / include-91
:ARG2 (c2 / carcinoma~e.18 :quant 58~e.16
:mod (o / ovary~e.17))
:ARG3 (p3 / percentage-entity :value 46.6~e.12))))
# ::id pmid_1901_8267.135 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The patients were stratified into two groups depending on the mutational status of KRAS @/@ BRAF @ .
# ::alignments 1-1.1.1.1 3-1 4-1.2.r 5-1.2.1 6-1.2 7-1.3 8-1.3.1.r 10-1.3.1.1 11-1.3.1 14-1.3.1.2.1.1.1 15-1.3.1.2 16-1.3.1.2.2.1.1
(s / stratify-01~e.3
:ARG1 (p2 / person
:ARG0-of (h / have-rel-role-91
:ARG2 (p / patient~e.1)))
:manner~e.4 (g / group~e.6 :quant 2~e.5)
:ARG0-of (d / depend-01~e.7
:ARG1~e.8 (s2 / status~e.11
:mod (m / mutate-01~e.10)
:poss (s3 / slash~e.15
:op1 (g2 / gene
:name (n / name :op1 "KRAS"~e.14))
:op2 (g3 / gene
:name (n2 / name :op1 "BRAF"~e.16))))))
# ::id pmid_1901_8267.136 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The relationships between KRAS @/@ BRAF mutations and clinicopathological factors , including p @-@ ERK1 @/@ 2 expression are shown in Table 2 @ .
# ::alignments 1-1.2.1 4-1.2.1.1.1.1.1.1 5-1.2.1.1.1 6-1.2.1.1.1.2.1.1 8-1.2.1.1 11-1.2.1.2 13-1.2.1.2.2 14-1.2.1.2.2.1.1.2 16-1.2.1.2.2.1.1.1.1 17-1.2.1.1.1 18-1.2.1.2.2.1.1.1.1 19-1.2.1.2.2.1 21-1 24-1.1 25-1.1.1
(s / show-01~e.21
:ARG0 (t / table~e.24 :mod 2~e.25)
:ARG1 (a2 / and
:op1 (r / relation-03~e.1
:ARG0 (m / mutate-01~e.8
:ARG1 (s2 / slash~e.5,17
:op1 (g / gene
:name (n / name :op1 "KRAS"~e.4))
:op2 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.6))))
:ARG2 (f / factor~e.11
:mod (c / clinicopathologic)
:ARG2-of (i / include-01~e.13
:ARG1 (e / express-03~e.19
:ARG2 (e2 / enzyme
:name (n3 / name :op1 "ERK1/2"~e.16,18)
:ARG3-of (p / phosphorylate-01~e.14))))))))
# ::id pmid_1901_8267.137 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok There was no significant correlation between KRAS @/@ BRAF mutations and the patient 's age .
# ::alignments 2-1.1 2-1.1.r 3-1.4 4-1 7-1.2.1.1.1.1 8-1.2.1 9-1.2.1.2.1.1 11-1.2 14-1.3.1.1.1 15-1.3.1.1 16-1.3
(c / correlate-01~e.4 :polarity~e.2 -~e.2
:ARG1 (m / mutate-01~e.11
:ARG1 (s2 / slash~e.8
:op1 (g / gene
:name (n / name :op1 "KRAS"~e.7))
:op2 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.9))))
:ARG2 (a / age-01~e.16
:ARG1 (p2 / person
:ARG0-of (h / have-rel-role-91~e.15
:ARG2 (p / patient~e.14))))
:ARG1-of (s / significant-02~e.3))
# ::id pmid_1901_8267.138 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The results in Table 2 show that KRAS @/@ BRAF mutation is correlated significantly with FIGO stage I , II ( P @ < 0.001 ) , and p @-@ ERK1 @/@ 2 ( P @ < 0.001 ) .
# ::alignments 1-1.1 1-1.1.1 1-1.1.1.r 4-1.1.1.1 5-1.1.1.1.1 7-1 10-1.2.1.1.1.1.1.1 11-1.2.1.1.1 12-1.2.1.1.1.2.1.1 14-1.2.1.1 16-1.2.1 16-1.2.2 17-1.2.3 18-1.2.1.2.r 19-1.2.1.2.3.1.1 20-1.2.1.2.1 20-1.2.1.2.2 21-1.2.1.2.1.1 23-1.2.1.2.2.1 26-1.2.1.3 26-1.2.2.3 28-1.2.1.3.1 29-1.2.1.3.1.1 32-1.2 32-1.2.1.2 33-1.2.1.3 33-1.2.2.2.2 35-1.2.2.2.1.1 36-1.2.1.1.1 37-1.2.2.2.1.1 40-1.2.1.3 40-1.2.2.2.2 42-1.2.1.3.1 43-1.2.1.3.1.1
(s / show-01~e.7
:ARG0 (t2 / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1
:location (t / table~e.4 :mod 2~e.5)))
:ARG1 (a / and~e.32
:op1 (c / correlate-01~e.16
:ARG1 (m / mutate-01~e.14
:ARG1 (s5 / slash~e.11,36
:op1 (g / gene
:name (n / name :op1 "KRAS"~e.10))
:op2 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.12))))
:ARG2~e.18 (a3 / and~e.32
:op1 (s3 / stage~e.20 :mod "I"~e.21)
:op2 (s4 / stage~e.20 :mod "II"~e.23)
:mod (o / organization
:name (n3 / name :op1 "FIGO"~e.19)))
:ARG1-of (s6 / statistical-test-91~e.26,33,40
:ARG2 (l / less-than~e.28,42 :op1 0.001~e.29,43)))
:op2 (c2 / correlate-01~e.16
:ARG1 m
:ARG2 (e / enzyme
:name (n4 / name :op1 "ERK1/2"~e.35,37)
:ARG3-of (p2 / phosphorylate-01~e.33,40))
:ARG1-of (s7 / statistical-test-91~e.26
:ARG2 l))
:ARG1-of (s2 / significant-02~e.17)))
# ::id pmid_1901_8267.139 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In addition , there were significant correlations between KRAS @/@ BRA @ F mutations and pathological grade ( P @ = 0.004 ) , and histological subtype ( P @ = 0.014 ) .
# ::alignments 0-1 0-1.1 0-1.1.r 1-1 1-1.1 1-1.1.r 5-1.1.3 6-1.1.1 6-1.1.2 9-1.1.1.1.1.1.1.1 10-1.1.1.1.1 14-1.1.1.1 16-1.1.1.2.1 17-1.1.1.2 20-1.1.1.3 23-1.1.1.3.1 26-1.1 27-1.1.2.2.1 28-1.1.2.2 31-1.1.2.3 34-1.1.2.3.1
(a / and~e.0,1
:op2~e.0,1 (a2 / and~e.0,1,26
:op1 (c / correlate-01~e.6
:ARG1 (m / mutate-01~e.14
:ARG1 (s3 / slash~e.10
:op1 (g / gene
:name (n / name :op1 "KRAS"~e.9))
:op2 (g2 / gene
:name (n2 / name :op1 "BRAF"))))
:ARG2 (g3 / grade~e.17
:mod (p / pathology~e.16))
:ARG1-of (s4 / statistical-test-91~e.20 :ARG2 0.004~e.23))
:op2 (c2 / correlate-01~e.6
:ARG1 m
:ARG2 (s2 / subtype~e.28
:mod (h / histology~e.27))
:ARG1-of (s5 / statistical-test-91~e.31 :ARG2 0.014~e.34))
:ARG1-of (s / significant-02~e.5)))
# ::id pmid_1901_8267.140 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Effect of KRAS @/@ BRAF mutations or p @-@ ERK1 @/@ 2 on the prognosis of ovarian carcinomas
# ::alignments 1-1 4-1.1.1.1.1.1.1 5-1.1.1.1 6-1.1.1.1.2.1.1 8-1.1.1 9-1.1 10-1.1.2.2 12-1.1.2.1.1 13-1.1.1.1 14-1.1.2.1.1 15-1.2.r 17-1.2 18-1.2.1.r 19-1.2.1.1 20-1.2.1
(a / affect-01~e.1
:ARG0 (o / or~e.9
:op1 (m / mutate-01~e.8
:ARG1 (s / slash~e.5,13
:op1 (g / gene
:name (n / name :op1 "KRAS"~e.4))
:op2 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.6))))
:op2 (e / enzyme
:name (n3 / name :op1 "ERK1/2"~e.12,14)
:ARG3-of (p2 / phosphorylate-01~e.10)))
:ARG1~e.15 (p / prognosis~e.17
:mod~e.18 (c / carcinoma~e.20
:mod (o2 / ovary~e.19))))
# ::id pmid_1901_8267.141 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Next , we examined the prognostic effect of KRAS @/@ BRAF mutations and p @-@ ERK1 @/@ 2 expression .
# ::alignments 0-1.3 2-1.1 3-1 5-1.2.2 6-1.2 9-1.2.1.1.1.1.1.1 10-1.2.1.1.1 11-1.2.1.1.1.2.1.1 13-1.2.1.1 14-1.2.1 15-1.2.1.2.1.2 17-1.2.1.2.1.1.1 18-1.2.1.1.1 19-1.2.1.2.1.1.1 20-1.2.1.2
(e / examine-01~e.3
:ARG0 (w / we~e.2)
:ARG1 (a / affect-01~e.6
:ARG0 (a2 / and~e.14
:op1 (m / mutate-01~e.13
:ARG1 (s / slash~e.10,18
:op1 (g / gene
:name (n / name :op1 "KRAS"~e.9))
:op2 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.11))))
:op2 (e2 / express-03~e.20
:ARG2 (e3 / enzyme
:name (n3 / name :op1 "ERK1/2"~e.17,19)
:ARG3-of (p2 / phosphorylate-01~e.15))))
:mod (p / prognostic~e.5))
:time (n4 / next~e.0))
# ::id pmid_1901_8267.142 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Out of the 58 samples that we examined , 45 were available for prognostic analysis .
# ::alignments 3-1.2.2.1.1 4-1.2.2.1 4-1.2.2.1.2 4-1.2.2.1.2.r 6-1.2.2.1.3.1 7-1.2.2.1.3 9-1.2.1 11-1 12-1.1.r 13-1.1.1 14-1.1
(a / available-02~e.11
:ARG1~e.12 (a2 / analyze-01~e.14
:mod (p / prognostic~e.13))
:ARG2 (t / thing :quant 45~e.9
:ARG1-of (i / include-91
:ARG2 (t2 / thing~e.4 :quant 58~e.3
:ARG2-of~e.4 (s2 / sample-01~e.4)
:ARG1-of (e / examine-01~e.7
:ARG0 (w / we~e.6))))))
# ::id pmid_1901_8267.143 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Kaplan @–@ Meier estimates of overall survival are plotted in Figure 3 @ .
# ::alignments 3-1.1 4-1.1.1.r 5-1.1.1.1 6-1.1.1 8-1 11-1.2 12-1.2.1
(p / plot-01~e.8
:ARG1 (e / estimate-01~e.3
:ARG1~e.4 (s / survive-01~e.6
:mod (o / overall~e.5))
:instrument (t / thing
:name (n / name :op1 "Kaplan–Meier")))
:medium (f / figure~e.11 :mod 3~e.12))
# ::id pmid_1901_8267.144 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok There was no significant relationship between KRAS @/@ BRAF mutations or p @-@ ERK1 @/@ 2 expression and overall survival in patients with ovarian carcinoma ( P @ = 0.2460 , P @ = 0.9339 , respectively ) .
# ::alignments 2-1.1 2-1.1.r 3-1.4 4-1 7-1.2.1.1.1.1.1 8-1.2.1.1 9-1.2.1.1.2.1.1 11-1.2.1 12-1.2 13-1.2.2.1.2 13-1.2.4 15-1.2.2.1.1.1 16-1.2.1.1 17-1.2.2.1.1.1 18-1.2.2 20-1.3.2 21-1.3 22-1.3.1.r 23-1.3.1.1.1 25-1.3.1.2.1.1 26-1.3.1.2.1 29-1.2.4 32-1.2.4.1 35-1.3.3 38-1.3.3.1 40-1.2.3
(r / relation-03~e.4 :polarity~e.2 -~e.2
:ARG0 (o4 / or~e.12
:op1 (m / mutate-01~e.11
:ARG1 (s3 / slash~e.8,16
:op1 (g / gene
:name (n / name :op1 "KRAS"~e.7))
:op2 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.9))))
:op2 (e / express-03~e.18
:ARG2 (e2 / enzyme
:name (n3 / name :op1 "ERK1/2"~e.15,17)
:ARG3-of (p / phosphorylate-01~e.13)))
:mod (r2 / respective~e.40)
:ARG1-of (s4 / statistical-test-91~e.13,29 :ARG2 0.2460~e.32))
:ARG2 (s2 / survive-01~e.21
:ARG0~e.22 (p5 / person
:ARG0-of (h / have-rel-role-91
:ARG2 (p2 / patient~e.23))
:ARG0-of (h2 / have-03
:ARG1 (c / carcinoma~e.26
:mod (o3 / ovary~e.25))))
:mod (o2 / overall~e.20)
:ARG1-of (s5 / statistical-test-91~e.35 :ARG2 0.9339~e.38))
:ARG1-of (s / significant-02~e.3))
# ::id pmid_1901_8267.145 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Univariate analysis showed that only FIGO stage III , IV affected the overall survival of patients with ovarian carcinoma significantly ( P @ = 0.014 ) .
# ::alignments 0-1.1.1 1-1.1 2-1 3-1.2.r 4-1.2.1.4 5-1.2.1.3.1.1 6-1.2.1.1 6-1.2.1.2 7-1.2.1.1.1 9-1.2.1.2.1 10-1.2 12-1.2.2.2 13-1.2.2 14-1.2.2.1.r 15-1.2.2.1.1.1 17-1.2.2.1.2.1.1 18-1.2.2.1.2.1 19-1.2.3 22-1.2.4 25-1.2.4.1
(s / show-01~e.2
:ARG0 (a / analyze-01~e.1
:mod (u / univariate~e.0))
:ARG1~e.3 (a2 / affect-01~e.10
:ARG0 (a3 / and
:op1 (s2 / stage~e.6 :mod "III"~e.7)
:op2 (s3 / stage~e.6 :mod "IV"~e.9)
:mod (o / organization
:name (n / name :op1 "FIGO"~e.5))
:mod (o4 / only~e.4))
:ARG1 (s4 / survive-01~e.13
:ARG0~e.14 (p3 / person
:ARG0-of (h2 / have-rel-role-91
:ARG2 (p / patient~e.15))
:ARG0-of (h / have-03
:ARG1 (c / carcinoma~e.18
:mod (o3 / ovary~e.17))))
:mod (o2 / overall~e.12))
:ARG1-of (s5 / significant-02~e.19)
:ARG1-of (s6 / statistical-test-91~e.22 :ARG2 0.014~e.25)))
# ::id pmid_1901_8267.146 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Effects of ERK1 @/@ 2 inactivation on ovarian carcinoma in vitro @
# ::alignments 1-1 2-1.1.r 3-1.1.2.1.1 5-1.1.2.1.1 6-1.1 6-1.1.1 6-1.1.1.r 7-1.2.r 8-1.2.1 9-1.2 11-1.3 12-1.3
(a / affect-01~e.1
:ARG0~e.2 (a2 / activate-01~e.6 :polarity~e.6 -~e.6
:ARG1 (e / enzyme
:name (n / name :op1 "ERK1/2"~e.3,5)))
:ARG1~e.7 (c / carcinoma~e.9
:mod (o / ovary~e.8))
:manner (i / in-vitro~e.11,12))
# ::id pmid_1901_8267.147 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok A panel of ovarian cancer cell lines and primary cultures of ovarian cancer were first analysed for KRAS and BRAF gene mutation status .
# ::alignments 1-1.1.1 2-1.1.1.1.r 3-1.1.1.1.1.2.1 4-1.1.1.1.1.2.2 5-1.1.1.1 6-1.1.1.1 7-1.1 8-1.1.2.2 9-1.1.2 11-1.1.1.1.1.2.1 12-1.1.1.1.1.2.2 12-1.1.2.1.2.1 14-1.2 15-1 18-1.3.1.1.1.1.1 20-1.3.1.1 22-1.3.1.1.2.1.1 24-1.3.1.1.1 24-1.3.1.1.2 25-1.3.1 26-1.3
(a / analyze-01~e.15
:ARG1 (a2 / and~e.7
:op1 (p / panel~e.1
:consist-of~e.2 (c / cell-line~e.5,6
:mod (d / disease :wiki "Ovarian_cancer"
:name (n / name :op1 "ovarian"~e.3,11 :op2 "cancer"~e.4,12))))
:op2 (c3 / culture-01~e.9
:ARG1 (d2 / disease :wiki "Cancer"
:name (n4 / name :op1 "cancer"~e.12))
:mod (p2 / primary~e.8)))
:time (f / first~e.14)
:purpose (s / status~e.26
:mod (m / mutate-01~e.25
:ARG1 (a4 / and~e.20
:op1 (g / gene~e.24
:name (n2 / name :op1 "KRAS"~e.18))
:op2 (g2 / gene~e.24
:name (n3 / name :op1 "BRAF"~e.22))))))
# ::id pmid_1901_8267.148 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Mutational status was correlated with growth inhibition and apoptosis induction by the MEK inhibitor CI @-@ 1040 that prevented activation of the downstream target , ERK1 @/@ 2 .
# ::alignments 0-1.2.1 1-1.2 3-1 4-1.3.r 5-1.3.1.1 6-1.3.1 7-1.3 8-1.3.2.1 9-1.3.2 10-1.1.r 12-1.1.2.1.1.1 13-1.1 13-1.1.2 13-1.1.2.r 14-1.1.1.1 16-1.1.1.1 18-1.1.3 19-1.1.3.1 20-1.1.3.1.1.r 22-1.1.3.1.1.2 23-1.1.3.1.1 25-1.1.3.1.1.1.1.1.1 27-1.1.3.1.1.1.1.1.1
(c / correlate-01~e.3
:ARG0~e.10 (s2 / small-molecule~e.13
:name (n2 / name :op1 "CI-1040"~e.14,16)
:ARG0-of~e.13 (i / inhibit-01~e.13
:ARG1 (p2 / protein-family
:name (n / name :op1 "MEK"~e.12)))
:ARG0-of (p / prevent-01~e.18
:ARG1 (a3 / activate-01~e.19
:ARG1~e.20 (t2 / target~e.23
:ARG1-of (m2 / mean-01
:ARG2 (e2 / enzyme
:name (n3 / name :op1 "ERK1/2"~e.25,27)))
:location (d / downstream~e.22)))))
:ARG1 (s / status~e.1
:mod (m / mutate-01~e.0))
:ARG2~e.4 (a / and~e.7
:op1 (i2 / inhibit-01~e.6
:ARG1 (g / grow-01~e.5))
:op2 (i3 / induce-01~e.9
:ARG2 (a2 / apoptosis~e.8))))
# ::id pmid_1901_8267.149 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Western blot analysis showed a dose @-@ dependent effect on the expression of active ERK1 @/@ 2 in ES2 cells , and active ERK1 @/@ 2 was not detectable 6 h after treating the cells with CI @-@ 1040 at a concentration of 5 μ @ M ( Figure 4 ) .
# ::alignments 0-1.1.1.1 1-1.1.1.1 2-1.1.1 3-1.1 5-1.1.2.2.1 7-1.1.2.2 8-1.1.2 9-1.1.2.1.r 11-1.1.2.1 14-1.1.2.1.1.1.1 16-1.1.2.1.1.1.1 18-1.1.2.1.1.3.1.1 19-1.1.2.1.1.3 23-1.1.2.1.1.1.1 25-1.1.2.1.1.1.1 27-1.2.1 27-1.2.1.r 28-1.2.2 29-1.2.2.2.2.1 30-1.2.2.2.2.2 31-1.2.2.2 32-1.2.2.2.1 34-1.2.2.2.1.1 35-1.2.2.2.1.2.r 36-1.2.2.2.1.2.1.1 38-1.2.2.2.1.2.1.1 41-1.2.2.2.1.2.2 43-1.2.2.2.1.2.2.1 52-1.3.1 53-1.3.1.1
(a / and
:op1 (s / show-01~e.3
:ARG0 (a2 / analyze-01~e.2
:manner (i / immunoblot-01~e.0,1))
:ARG1 (a3 / affect-01~e.8
:ARG1~e.9 (e / express-03~e.11
:ARG2 (e2 / enzyme
:name (n3 / name :op1 "ERK1/2"~e.14,16,23,25)
:ARG1-of (a4 / activate-01)
:location (c / cell-line~e.19
:name (n4 / name :op1 "ES2"~e.18))))
:ARG0-of (d / depend-01~e.7
:ARG1 (d2 / dose~e.5))))
:op2 (p / possible-01 :polarity~e.27 -~e.27
:ARG1 (d3 / detect-01~e.28
:ARG1 e2
:time (a5 / after~e.31
:op1 (t3 / treat-04~e.32
:ARG1 c~e.34
:ARG2~e.35 (s2 / small-molecule
:name (n5 / name :op1 "CI-1040"~e.36,38)
:quant (c3 / concentration-quantity~e.41 :quant 5~e.43
:unit (m / micromolar))))
:quant (t2 / temporal-quantity :quant 6~e.29
:unit (h / hour~e.30)))))
:ARG1-of (d4 / describe-01
:ARG0 (f / figure~e.52 :mod 4~e.53)))
# ::id pmid_1901_8267.150 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok As shown in Figure 5 , four of the tumours harbouring either KRAS or BRAF mutations showed a marked reduction (< 50 % of DMSO control ) in the cell number in the CI @-@ 1040 @-@ treated group as compared with the other 14 tumours containing wild @-@ type KRAS and BRAF ( P @ < 0.001 ) .
# ::alignments 1-1 1-1.3 1-1.3.r 4-1.3.1 5-1.3.1.1 8-1.1.1 11-1.1 11-1.1.2.1 12-1.1.2.1.1 15-1.1.2.1.1.1.1.1.1.1 17-1.1.2.1.1.1 19-1.1.2.1.1.1.2.1.1.1 21-1.1.2.1.1.1.1 21-1.1.2.1.1.1.2 22-1 24-1.2.3 25-1.2 27-1.2.2.1.1 28-1.2.2.1 29-1.2.2.1.2.r 30-1.2.2.1.2.1.1.1 31-1.2.2.1.2 33-1.2.1.r 35-1.2.1.1 36-1.2.1 37-1.2.4.r 39-1.2.4.1.1.1.1 41-1.2.4.1.1.1.1 43-1.2.4.1 44-1.2.4 46-1.2.5.r 49-1.2.5.2 50-1.2.5.1 51-1.2.5 52-1.2.5.3 53-1.2.5.3.1.1.2 55-1.2.5.3.1.1.2 57-1.2.5.3.1.1.1.1 59-1.2.5.3.1 61-1.1.2.1.1.1.2.1.1.1 61-1.2.5.3.1.2.1.1 65-1.4 67-1.2.2 67-1.4.1 68-1.4.1.1
(s / show-01~e.1,22
:ARG0 (t / tumor~e.11 :quant 4~e.8
:ARG1-of (i / include-01
:ARG2 (t2 / tumor~e.11
:ARG0-of (h / harbor-01~e.12
:ARG1 (o / or~e.17
:op1 (m / mutate-01~e.21
:ARG1 (g / gene
:name (n / name :op1 "KRAS"~e.15)))
:op2 (m2 / mutate-01~e.21
:ARG1 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.19,61))))))))
:ARG1 (r / reduce-01~e.25
:ARG1~e.33 (n4 / number~e.36
:quant-of (c2 / cell~e.35))
:ARG2 (l / less-than~e.67
:op1 (p / percentage-entity~e.28 :value 50~e.27
:quant-of~e.29 (c / control~e.31
:mod (s4 / small-molecule
:name (n3 / name :op1 "DMSO"~e.30)))))
:ARG1-of (m3 / mark-01~e.24)
:location~e.37 (g3 / group~e.44
:ARG1-of (t3 / treat-04~e.43
:ARG2 (s2 / small-molecule
:name (n5 / name :op1 "CI-1040"~e.39,41))))
:compared-to~e.46 (t4 / tumor~e.51 :quant 14~e.50
:mod (o2 / other~e.49)
:ARG0-of (c3 / contain-01~e.52
:ARG1 (a / and~e.59
:op1 (g4 / gene
:name (n6 / name :op1 "KRAS"~e.57)
:mod (w / wild-type~e.53,55))
:op2 (g5 / gene
:name (n7 / name :op1 "BRAF"~e.61)
:mod w)))))
:ARG1-of~e.1 (s3 / show-01~e.1
:ARG0 (f / figure~e.4 :mod 5~e.5))
:ARG1-of (s5 / statistical-test-91~e.65
:ARG2 (l2 / less-than~e.67 :op1 0.001~e.68)))
# ::id pmid_1901_8267.151 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok CI @-@ 1040 had no significant effect on the growth of normal cells , including the OSE cells .
# ::alignments 0-1.2.1.1 2-1.2.1.1 4-1.1 4-1.1.r 5-1.4 6-1 7-1.3.r 9-1.3 10-1.3.1.r 11-1.3.1.1 12-1.3.1 12-1.3.1.2.1 14-1.3.1.2 17-1.3.1
(a / affect-01~e.6 :polarity~e.4 -~e.4
:ARG0 (s2 / small-molecule
:name (n / name :op1 "CI-1040"~e.0,2))
:ARG1~e.7 (g / grow-01~e.9
:ARG1~e.10 (c / cell~e.12,17
:ARG1-of (n2 / normal-02~e.11)
:ARG2-of (i / include-01~e.14
:ARG1 (c2 / cell~e.12
:source (e / epithelium
:location (s3 / surface)
:part-of (o / ovary))))))
:ARG1-of (s / significant-02~e.5))
# ::id pmid_1901_8267.152 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok It is likely that KRAS @/@ BRAF mutation is not the only determinant for activating ERK1 @/@ 2 .
# ::alignments 2-1 5-1.1.2.1.1.1.1 6-1.1.2.1 7-1.1.2.1.2.1.1 9-1.1.2 11-1.1.1 11-1.1.1.r 13-1.1.4 16-1.1.3 17-1.1.3.1.1.1 18-1.1.2.1 19-1.1.3.1.1.1
(l / likely-01~e.2
:ARG1 (d / determine-01 :polarity~e.11 -~e.11
:ARG0 (m / mutate-01~e.9
:ARG1 (s / slash~e.6,18
:op1 (g / gene
:name (n / name :op1 "KRAS"~e.5))
:op2 (g2 / gene
:name (n2 / name :op1 "BRAF"~e.7))))
:ARG1 (a / activate-01~e.16
:ARG1 (e / enzyme
:name (n3 / name :op1 "ERK1/2"~e.17,19)))
:mod (o / only~e.13)))
# ::id pmid_1901_8267.153 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Therefore , we analysed p @-@ ERK1 @/@ 2 expression in each of the cell lines listed in Figure 5 @ .
# ::alignments 0-1 2-1.1.1 3-1.1 4-1.1.2.1.2 6-1.1.2.1.1.1 8-1.1.2.1.1.1 9-1.1.2 10-1.1.2.2.r 11-1.1.2.2.1 14-1.1.2.2 15-1.1.2.2 16-1.1.2.2.2 19-1.1.2.2.2.1 20-1.1.2.2.2.1.1
(c / cause-01~e.0
:ARG1 (a / analyze-01~e.3
:ARG0 (w / we~e.2)
:ARG1 (e / express-03~e.9
:ARG2 (e2 / enzyme
:name (n / name :op1 "ERK1/2"~e.6,8)
:ARG3-of (p / phosphorylate-01~e.4))
:ARG3~e.10 (c2 / cell-line~e.14,15
:mod (e3 / each~e.11)
:ARG1-of (l / list-01~e.16
:ARG2 (f / figure~e.19 :mod 5~e.20))))))
# ::id pmid_1901_8267.154 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Only four of these cell lines , MDAH2774 , ES2 , MPSC1 , and POC1 , strongly expressed p @-@ ERK1 @/@ 2 .
# ::alignments 0-1.2.2 1-1.2.1 3-1.2.3.1.1 4-1.2 4-1.2.3.1 5-1.2.3.1 7-1.2.4.1.1.1.1 9-1.2.4.1.2.1.1 11-1.2.4.1.3.1.1 13-1.2.4.1 14-1.2.4.1.4.1.1 16-1.3 17-1 18-1.1.2 20-1.1.1.1 22-1.1.1.1
(e / express-03~e.17
:ARG2 (e2 / enzyme
:name (n5 / name :op1 "ERK1/2"~e.20,22)
:ARG3-of (p / phosphorylate-01~e.18))
:ARG3 (c / cell-line~e.4 :quant 4~e.1
:mod (o / only~e.0)
:ARG1-of (i / include-91
:ARG2 (c2 / cell-line~e.4,5
:mod (t / this~e.3)))
:ARG1-of (m / mean-01
:ARG2 (a / and~e.13
:op1 (c3 / cell-line
:name (n / name :op1 "MDAH2774"~e.7))
:op2 (c4 / cell-line
:name (n2 / name :op1 "ES2"~e.9))
:op3 (c5 / cell-line
:name (n3 / name :op1 "MPSC1"~e.11))
:op4 (c6 / cell-line
:name (n4 / name :op1 "POC1"~e.14)))))
:ARG1-of (s / strong-02~e.16))
# ::id pmid_1901_8267.155 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok SKOV3 and A2780 showed weak expression of ERK1 @/@ 2.These results suggest that activation of ERK1 @/@ 2 may depend on KRAS @/@ BRAF mutation in ovarian cancer cells .
# ::alignments 0-1.1.1.1.1.1 1-1.1.1 2-1.1.1.2.1.1 3-1.1 4-1.1.2.2 5-1.1.2 6-1.1.2.1.r 7-1.1.2.1.1.1 8-1.2.2.1.2.1 10-1.2.1 10-1.2.1.1 10-1.2.1.1.r 11-1.2 13-1.2.2.1.1 14-1.2.2.1.1.1.r 15-1.2.2.1.1.1.1.1 16-1.2.2.1.2.1 17-1.2.2.1.1.1.1.1 18-1.2.2 19-1.2.2.1 22-1.2.2.1.2.1.1.1.1 23-1.2.2.1.2.1 24-1.2.2.1.2.1.2.1.1 26-1.2.2.1.2 27-1.2.2.1.2.2.r 28-1.2.2.1.2.2.1.2.1 29-1.2.2.1.2.2.1.2.2 30-1.2.2.1.2.2
(m / multi-sentence
:snt1 (s / show-01~e.3
:ARG0 (a / and~e.1
:op1 (c / cell-line
:name (n2 / name :op1 "SKOV3"~e.0))
:op2 (c2 / cell-line
:name (n3 / name :op1 "A2780"~e.2)))
:ARG1 (e / express-03~e.5
:ARG2~e.6 (e2 / enzyme
:name (n4 / name :op1 "ERK1/2"~e.7))
:ARG1-of (w / weak-02~e.4)))
:snt2 (s2 / suggest-01~e.11
:ARG0 (t2 / thing~e.10
:ARG2-of~e.10 (r / result-01~e.10)
:mod (t / this))
:ARG1 (p / possible-01~e.18
:ARG1 (d2 / depend-01~e.19
:ARG0 (a2 / activate-01~e.13
:ARG1~e.14 (e3 / enzyme
:name (n5 / name :op1 "ERK1/2"~e.15,17)))
:ARG1 (m2 / mutate-01~e.26
:ARG1 (s3 / slash~e.8,16,23
:op1 (g / gene
:name (n6 / name :op1 "KRAS"~e.22))
:op2 (g2 / gene
:name (n7 / name :op1 "BRAF"~e.24)))
:location~e.27 (c3 / cell~e.30
:mod (d / disease :wiki "Ovarian_cancer"
:name (n / name :op1 "ovarian"~e.28 :op2 "cancer"~e.29))))))))
# ::id pmid_1901_8267.156 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To assess the mechanisms underlying growth inhibition by CI @-@ 1040 , we measured the percentages of BrdUrd @-@ labelled cells and Annexin V @-@ labelled cells to estimate proliferation and apoptosis , respectively .
# ::alignments 1-1.4 3-1.4.2 4-1.4.2.1 5-1.4.2.1.1.2 6-1.4.2.1.1 7-1.4.2.1.1.1.r 8-1.4.2.1.1.1.1.1 10-1.4.2.1.1.1.1.1 12-1.1 13-1 15-1.2.1 15-1.2.2 17-1.2.1.1.1.1.1.1.1 19-1.2.1.1.1.1 19-1.2.2.1.1.1 20-1.2.1.1.1 20-1.2.2.1.1 21-1.2 22-1.2.2.1.1.1.1.1.1 23-1.2.2.1.1.1.1.1.2 25-1.2.1.1.1.1 25-1.2.2.1.1.1 26-1.2.1.1.1 26-1.2.2.1.1 28-1.3 29-1.3.2.1 30-1.3.2 31-1.3.2.2 33-1.3.2.3
(m / measure-01~e.13
:ARG0 (w / we~e.12)
:ARG1 (a / and~e.21
:op1 (p / percentage~e.15
:ARG3-of (i3 / include-91
:ARG1 (c / cell~e.20,26
:ARG1-of (l / label-01~e.19,25
:ARG0 (s2 / small-molecule
:name (n / name :op1 "BrdUrd"~e.17))))))
:op2 (p2 / percentage~e.15
:ARG3-of (i2 / include-91
:ARG1 (c2 / cell~e.20,26
:ARG1-of (l2 / label-01~e.19,25
:ARG0 (p4 / protein
:name (n2 / name :op1 "Annexin"~e.22 :op2 "V"~e.23)))))))
:purpose (e / estimate-01~e.28
:ARG0 w
:ARG1 (a2 / and~e.30
:op1 (p3 / proliferate-01~e.29)
:op2 (a3 / apoptosis~e.31)
:mod (r / respective~e.33)))
:purpose (a4 / assess-01~e.1
:ARG0 w
:ARG1 (m4 / mechanism~e.3
:ARG0-of (u / underlie-01~e.4
:ARG1 (i / inhibit-01~e.6
:ARG0~e.7 (s / small-molecule
:name (n3 / name :op1 "CI-1040"~e.8,10))
:ARG1 (g / grow-01~e.5))))))
# ::id pmid_1901_8267.157 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We found that CI @-@ 1040 significantly reduced cellular proliferation and induced apoptosis in cell lines with either KRAS or BRAF mutations in comparison with cell lines with wild @-@ type sequences ( Figure 6 , Supplementary Figure 1 ) .
# ::alignments 0-1.1 1-1 2-1.2.r 3-1.2.1.1.1.1 5-1.2.1.1.1.1 6-1.2.1.3 7-1.2.1 8-1.2.1.2.1 9-1.2.1.2 10-1.2 11-1.2.2 12-1.2.2.2 14-1.2.3 14-1.2.3.2 15-1.2.3 15-1.2.3.2 19-1.2.3.1.1.1.1.1.1 21-1.2.3.1.1 23-1.2.3.1.1.2.1.1.1 25-1.2.3.1.1.1 25-1.2.3.1.1.2 27-1.2.3.2.r 29-1.2.3.2 30-1.2.3.2 32-1.2.3.2.1.1.1 34-1.2.3.2.1.1.1 35-1.2.3.2.1.1 38-1.3.1.1 39-1.3.1.1.1 43-1.3.1.2.2 44-1.3.1.2 45-1.3.1.2.1
(f / find-01~e.1
:ARG0 (w / we~e.0)
:ARG1~e.2 (a2 / and~e.10
:op1 (r / reduce-01~e.7
:ARG0 (s / small-molecule
:name (n / name :op1 "CI-1040"~e.3,5))
:ARG1 (p / proliferate-01~e.9
:ARG0 (c / cell~e.8))
:ARG2 (s2 / significant-02~e.6))
:op2 (i / induce-01~e.11
:ARG0 s
:ARG2 (a / apoptosis~e.12))
:location (c2 / cell-line~e.14,15
:ARG0-of (h / have-03
:ARG1 (o / or~e.21
:op1 (m / mutate-01~e.25
:ARG1 (g / gene
:name (n2 / name :op1 "KRAS"~e.19)))
:op2 (m2 / mutate-01~e.25
:ARG1 (g2 / gene
:name (n3 / name :op1 "BRAF"~e.23)))))
:compared-to~e.27 (c3 / cell-line~e.14,15,29,30
:ARG0-of (h2 / have-03
:ARG1 (s3 / sequence~e.35
:mod (w2 / wild-type~e.32,34))))))
:ARG1-of (d / describe-01
:ARG0 (a3 / and
:op1 (f2 / figure~e.38 :mod 6~e.39)
:op2 (f3 / figure~e.44 :mod 1~e.45
:ARG1-of (s4 / supplement-01~e.43)))))
# ::id pmid_1901_8267.158 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Effects of CI @-@ 1040 ERK1 @/@ 2 inactivation on ovarian carcinomas in vivo @
# ::alignments 1-1 2-1.1.r 3-1.1.2.1.1 5-1.1.2.1.1 6-1.1.3.1.1 8-1.1.3.1.1 9-1.1 9-1.1.1 9-1.1.1.r 10-1.2.r 11-1.2.1 12-1.2 14-1.3 15-1.3
(a / affect-01~e.1
:ARG0~e.2 (a2 / activate-01~e.9 :polarity~e.9 -~e.9
:ARG0 (s / small-molecule
:name (n2 / name :op1 "CI-1040"~e.3,5))
:ARG1 (e / enzyme
:name (n / name :op1 "ERK1/2"~e.6,8)))
:ARG1~e.10 (c / carcinoma~e.12
:mod (o / ovary~e.11))
:manner (i / in-vivo~e.14,15))
# ::id pmid_1901_8267.159 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok On the basis of the above findings , we investigated whether CI @-@ 1040 had a growth @-@ inhibitory effect on tumour formation and development in vivo @ .
# ::alignments 2-1.3 3-1.3.1.r 5-1.3.1.2 6-1.3.1 6-1.3.1.1 6-1.3.1.1.r 8-1.1 9-1 10-1.2.1 10-1.2.1.r 11-1.2.2.1.1 13-1.2.2.1.1 16-1.2.4.2 18-1.2.4 19-1.2 20-1.2.3.r 21-1.2.3.1.1 22-1.2.3.1 23-1.2.3 24-1.2.3.2 26-1.2.5 27-1.2.5
(i / investigate-01~e.9
:ARG0 (w / we~e.8)
:ARG1 (a / affect-01~e.19 :mode~e.10 interrogative~e.10
:ARG0 (s / small-molecule
:name (n / name :op1 "CI-1040"~e.11,13))
:ARG1~e.20 (a2 / and~e.23
:op1 (f / form-01~e.22
:ARG1 (t / tumor~e.21))
:op2 (d / develop-01~e.24
:ARG2 t))
:ARG2 (i3 / inhibit-01~e.18
:ARG0 s
:ARG1 (g / grow-01~e.16))
:manner (i2 / in-vivo~e.26,27))
:ARG1-of (b / base-02~e.2
:ARG0~e.3 (t2 / thing~e.6
:ARG1-of~e.6 (f2 / find-01~e.6)
:mod (a3 / above~e.5))))
# ::id pmid_1901_8267.160 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Tumour xenografts from both MDAH2774 ( KRAS mutant ) and SKOV3 ( wild type of KRAS and BRAF ) cell lines were established in a nu @ / @ nu mouse model .
# ::alignments 0-1.1.1.1 1-1.1.1 1-1.1.2 2-1.1.1.2.r 4-1.1.1.2.1.1 7-1.1.1.2.2.1.1.1 9-1.1.1.2.2.1 9-1.1.1.2.2.1.2 9-1.1.1.2.2.1.2.r 11-1.1 12-1.1.2.2.1.1 14-1.1.2.2.2.1.1.2 15-1.1.2.2.2.1.1.2 18-1.1.2.2.2.1.1.1.1 20-1.1.2.2.2.1 22-1.1.2.2.2.1.2.1.1 25-1.1.1.2 25-1.1.2.2 26-1.1.1.2 28-1 38-1.2.1 39-1.2
(e / establish-01~e.28
:ARG1 (a2 / and~e.11
:op1 (x / xenograft~e.1
:mod (t / tumor~e.0)
:source~e.2 (c / cell-line~e.25,26
:name (n / name :op1 "MDAH2774"~e.4)
:ARG1-of (m4 / mean-01
:ARG2 (g / gene~e.9
:name (n2 / name :op1 "KRAS"~e.7)
:ARG2-of~e.9 (m / mutate-01~e.9)))))
:op2 (x2 / xenograft~e.1
:mod t
:source (c2 / cell-line~e.25
:name (n3 / name :op1 "SKOV3"~e.12)
:ARG1-of (m5 / mean-01
:ARG2 (a / and~e.20
:op1 (g2 / gene
:name (n4 / name :op1 "KRAS"~e.18)
:mod (w / wild-type~e.14,15))
:op2 (g3 / gene
:name (n5 / name :op1 "BRAF"~e.22)
:mod w))))))
:location (m2 / model~e.39
:mod (m3 / mouse~e.38
:mod (n6 / nude))))
# ::id pmid_1901_8267.161 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok All mice injected with CI @-@ 1040 developed significantly smaller intra @-@ abdominal xenograft tumours than the mice carrying diluent control cells of the KRAS mutant cell line MADH2774 ( Figure 7A ) .
# ::alignments 0-1.1.1 1-1.1 2-1.1.2 3-1.1.2.1.r 4-1.1.2.1.1.1 6-1.1.2.1.1.1 7-1 8-1.2.4 9-1.2.3 9-1.2.3.1 9-1.2.3.1.r 10-1.2.2 12-1.2.2 13-1.2.1 14-1.2 15-1.3.r 17-1.3 18-1.3.1 19-1.3.1.1.2 20-1.3.1.1.1 21-1.3.1.1 25-1.3.1.1.3.2.1.1 27-1.3.1.1.3.2 27-1.3.1.1.3.2.2 27-1.3.1.1.3.2.2.r 28-1.3.1.1.3 29-1.3.1.1.3 30-1.3.1.1.3.1.1 33-1.4.1 34-1.4.1.1
(d / develop-01~e.7
:ARG1 (m / mouse~e.1
:mod (a / all~e.0)
:ARG2-of (i / inject-01~e.2
:ARG1~e.3 (s / small-molecule
:name (n / name :op1 "CI-1040"~e.4,6))))
:ARG2 (t / tumor~e.14
:mod (x / xenograft~e.13)
:mod (i2 / intra-abdominal~e.10,12)
:mod (s2 / small~e.9
:degree~e.9 (m2 / more~e.9))
:ARG1-of (s3 / significant-02~e.8))
:compared-to~e.15 (m3 / mouse~e.17
:ARG0-of (c / carry-01~e.18
:ARG1 (c2 / cell~e.21
:mod (c3 / control~e.20)
:mod (d2 / diluent~e.19)
:poss (c4 / cell-line~e.28,29
:name (n2 / name :op1 "MADH2774"~e.30)
:mod (g / gene~e.27
:name (n3 / name :op1 "KRAS"~e.25)
:ARG2-of~e.27 (m4 / mutate-01~e.27))))))
:ARG1-of (d3 / describe-01
:ARG0 (f / figure~e.33 :mod "7A"~e.34)))
# ::id pmid_1901_8267.162 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok There were no differences in intra @-@ abdominal xenograft tumour weights between the CI @-@ 1040 @-@ treated group and control groups transplanted with the wild @-@ type KRAS @/@ BRA @ F cell line SKOV3 ( Figure 7B ) .
# ::alignments 2-1.1 2-1.1.r 3-1 4-1.4.r 5-1.4.1.2 7-1.4.1.2 8-1.4.1.1 9-1.4.1 10-1.4 13-1.2.1.1.2.1 15-1.2.1.1.2.1 17-1.2.1 18-1.2 20-1.3.1 21-1.3 22-1.3.2 23-1.3.2.1.r 25-1.3.2.1.3.1.1.3 27-1.3.2.1.3.1.1.3 29-1.3.2.1.3.1.1.2.1 30-1.3.2.1.3.1 34-1.3.2.1 35-1.3.2.1 36-1.3.2.1.2.1 39-1.5.1 40-1.5.1.1
(d / differ-02~e.3 :polarity~e.2 -~e.2
:ARG1 (g / group~e.18
:ARG1-of (t / treat-04~e.17
:ARG2 (s / small-molecule :wiki -
:name (n / name :op1 "CI-1040"~e.13,15))))
:ARG2 (g2 / group~e.21
:mod (c / control~e.20)
:ARG2-of (t2 / transplant-01~e.22
:ARG1~e.23 (c2 / cell-line~e.34,35 :wiki -
:name (n2 / name :op1 "SKOV3"~e.36)
:mod (g5 / gene
:mod (s2 / slash~e.30
:op1 (g3 / gene :wiki -
:name (n3 / name :op1 "KRAS"~e.29)
:mod (w / wild-type~e.25,27))
:op2 (g4 / gene :wiki "BRAF_(gene)"
:name (n4 / name :op1 "BRAF")
:mod w))))))
:ARG3~e.4 (w2 / weight-01~e.10
:ARG1 (t3 / tumor~e.9
:mod (x / xenograft~e.8)
:mod (i / intra-abdominal~e.5,7)))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.39 :mod "7B"~e.40)))
# ::id pmid_1901_8267.163 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Histological examination of the tumours after CI @-@ 1040 treatment showed inactivation of p @-@ ERK1 @/@ 2 in tumour cells based on immunohistochemistry ( Figure 7C and D ) .
# ::alignments 1-1.1 2-1.1.1.r 4-1.1.1 5-1.1.3 6-1.1.3.1.1.1.1 8-1.1.3.1.1.1.1 9-1.1.3.1 10-1 11-1.2 11-1.2.1 11-1.2.1.r 12-1.2.2.r 13-1.2.2.2 15-1.2.2.1.1 17-1.2.2.1.1 18-1.2.3.r 19-1.2.3.1 20-1.2.3 21-1.2.4 22-1.2.4.1.r 23-1.2.4.1 26-1.3.1.1 26-1.3.1.2 27-1.3.1.1.1 28-1.3.1
(s / show-01~e.10
:ARG0 (e / examine-01~e.1
:ARG1~e.2 (t / tumor~e.4)
:mod (h / histologic)
:time (a / after~e.5
:op1 (t2 / treat-04~e.9
:ARG2 (s2 / small-molecule
:name (n / name :op1 "CI-1040"~e.6,8)))))
:ARG1 (a2 / activate-01~e.11 :polarity~e.11 -~e.11
:ARG1~e.12 (e2 / enzyme
:name (n2 / name :op1 "ERK1/2"~e.15,17)
:ARG3-of (p / phosphorylate-01~e.13))
:location~e.18 (c / cell~e.20
:mod t~e.19)
:ARG1-of (b / base-02~e.21
:ARG2~e.22 (i / immunohistochemistry~e.23)))
:ARG1-of (d / describe-01
:ARG0 (a3 / and~e.28
:op1 (f / figure~e.26 :mod "7C"~e.27)
:op2 (f2 / figure~e.26 :mod "7D"))))
# ::id pmid_1956_8237.1 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Episodic Src activation in uveal melanoma revealed by kinase activity profiling ( PMID : 19568237 )
# ::alignments 0-1.5 1-1.1.1.1 2-1 3-1.2.r 4-1.2.2 5-1.2.1.1 6-1.3 7-1.3.1.r 8-1.3.1.1.1 9-1.3.1.1 10-1.3.1
(a / activate-01~e.2
:ARG1 (p / protein
:name (n / name :op1 "Src"~e.1))
:location~e.3 (m / medical-condition
:name (n2 / name :op1 "melanoma"~e.5)
:mod (u / uveal~e.4))
:ARG1-of (r / reveal-01~e.6
:ARG0~e.7 (p2 / profile-01~e.10
:ARG1 (a2 / activity-06~e.9
:ARG0 (k / kinase~e.8))))
:ARG1-of (d2 / describe-01
:ARG0 (p3 / publication-91 :ARG8 "PMID19568237"))
:mod (e / episodic~e.0))
# ::id pmid_1956_8237.8 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Results :
# ::alignments 1-1 1-1.1 1-1.1.r
(t / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1))
# ::id pmid_1956_8237.9 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We identified Src as a kinase that is associated with ERK1 @/@ 2 activation in UM .
# ::alignments 0-1.1 1-1 2-1.2.1.1 3-1.3.r 5-1.3 8-1.3.1 9-1.3.1.1.r 10-1.3.1.1.1.1.1 12-1.3.1.1.1.1.1 13-1.3.1.1
(i / identify-01~e.1
:ARG0 (w / we~e.0)
:ARG1 (p / protein
:name (n / name :op1 "Src"~e.2))
:ARG2~e.3 (k / kinase~e.5
:ARG1-of (a / associate-01~e.8
:ARG2~e.9 (a2 / activate-01~e.13
:ARG1 (e / enzyme
:name (n2 / name :op1 "ERK1/2"~e.10,12))
:location (m / medical-condition
:name (n3 / name :op1 "melanoma")
:mod (u / uveal))))))
# ::id pmid_1956_8237.10 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok However , low Src levels and reduced ERK1 @/@ 2 activation in metastatic cell lines suggest that proliferation in metastases can become independent of Src and RAS/RAF/MEK/ERK signalling .
# ::alignments 0-1 2-1.1.1.1.1 3-1.1.1.1.2.1.1 4-1.1.1.1 5-1.1.1 6-1.1.1.2.2 7-1.1.1.2.1.1.1 9-1.1.1.2.1.1.1 10-1.1.1.2 12-1.1.1.3.1 13-1.1.1.3 14-1.1.1.3 15-1.1 16-1.1.2.r 17-1.1.2.1.1 18-1.1.2.1.1.1.r 19-1.1.2.1.1.1 20-1.1.2 21-1.1.2.1 22-1.1.2.1.2 22-1.1.2.1.2.1 22-1.1.2.1.2.1.r 23-1.1.2.1.2.3.r 24-1.1.2.1.2.3.1 25-1.1.2.1.2.3 26-1.1.2.1.2.3.2.1.1.1 27-1.1.2.1.2.3.2
(h / have-concession-91~e.0
:ARG1 (s / suggest-01~e.15
:ARG0 (a / and~e.5
:op1 (l / level~e.4
:ARG1-of (l2 / low-04~e.2)
:quant-of (p / protein
:name (n / name :op1 "Src"~e.3)))
:op2 (a4 / activate-01~e.10
:ARG1 (e / enzyme
:name (n2 / name :op1 "ERK1/2"~e.7,9))
:ARG1-of (r / reduce-01~e.6))
:location (c / cell-line~e.13,14
:ARG1-of (m / metastasize-101~e.12)))
:ARG1~e.16 (p2 / possible-01~e.20
:ARG1 (b / become-01~e.21
:ARG1 (p3 / proliferate-01~e.17
:location~e.18 m~e.19)
:ARG2 (d / depend-01~e.22 :polarity~e.22 -~e.22
:ARG0 p3
:ARG1~e.23 (a3 / and~e.25
:op1 p~e.24
:op2 (s2 / signal-07~e.27
:ARG0 (p4 / pathway
:name (n3 / name :op1 "RAS/RAF/MEK/ERK"~e.26)))))))))
# ::id pmid_1956_8237.11 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Inhibition of Src led to the growth reduction of primary UM cultures and cell lines , whereas metastatic cell line growth was only slightly reduced .
# ::alignments 0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.1.1 3-1.1 4-1.1.2.r 6-1.1.2.1 7-1.1.2 8-1.1.2.1.1.r 9-1.1.2.1.1.1.2 11-1.1.2.1.1.2 12-1.1.2.1.1 13-1.1.2.1.1.1 14-1.1.2.1.1.1 16-1 17-1.2.1.1.1 18-1.2.1.1 19-1.2.1.1 20-1.2.1 22-1.2.2 23-1.2.3 24-1.2
(c / contrast-01~e.16
:ARG1 (l / lead-03~e.3
:ARG0 (i / inhibit-01~e.0
:ARG1~e.1 (p / protein
:name (n / name :op1 "Src"~e.2)))
:ARG2~e.4 (r / reduce-01~e.7
:ARG1 (g / grow-01~e.6
:ARG1~e.8 (a / and~e.12
:op1 (c2 / cell-line~e.13,14
:mod (m2 / medical-condition
:name (n2 / name :op1 "melanoma")
:mod (u / uveal))
:mod (p2 / primary~e.9))
:op2 (c3 / culture-01~e.11
:mod m2
:mod p2)))))
:ARG2 (r2 / reduce-01~e.24
:ARG1 (g2 / grow-01~e.20
:ARG1 (c4 / cell-line~e.18,19
:ARG1-of (m / metastasize-101~e.17)))
:mod (o / only~e.22)
:degree (s / slight~e.23)))
# ::id pmid_1956_8237.92 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Results
# ::alignments 1-1 1-1.1 1-1.1.r
(t / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1))
# ::id pmid_1956_8237.93 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok ERK1 @/@ 2 activation in UM
# ::alignments 1-1.1.1.1 3-1.1.1.1 4-1
(a / activate-01~e.4
:ARG1 (e / enzyme
:name (n / name :op1 "ERK1/2"~e.1,3))
:location (m / medical-condition
:name (n2 / name :op1 "melanoma")
:mod (u / uveal)))
# ::id pmid_1956_8237.94 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok An antibody array was applied to investigate the MAPK pathway in 10 UM cell lines , in three primary UM and three UM metastasis .
# ::alignments 1-1.1.1 2-1.1 4-1 6-1.2 8-1.2.1.1.1 9-1.2.1 10-1.2.2.r 11-1.2.2.1.1 13-1.2.2.1 14-1.2.2.1 17-1.2.2.2.1 17-1.2.2.3.1 18-1.2.2.2.4 20-1.2.2 21-1.2.2.2.1 21-1.2.2.3.1 23-1.2.2.3
(a / apply-03~e.4
:ARG1 (a2 / array-01~e.2
:ARG1 (a3 / antibody~e.1))
:purpose (i / investigate-01~e.6
:ARG1 (p / pathway~e.9
:name (n / name :op1 "MAPK"~e.8))
:location~e.10 (a4 / and~e.20
:op1 (c / cell-line~e.13,14 :quant 10~e.11
:mod (m2 / medical-condition
:name (n2 / name :op1 "melanoma")
:mod (u / uveal)))
:op2 (m3 / medical-condition :quant 3~e.17,21
:name (n3 / name :op1 "melanoma")
:mod u
:mod (p2 / primary~e.18))
:op3 (m / metastasize-101~e.23 :quant 3~e.17,21
:mod m2))))
# ::id pmid_1956_8237.95 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We observed a uniform HSP27 phosphorylation , with the exception of in three UM cell lines ( OCM1 , -@ 3 , -@ 8 ) .
# ::alignments 0-1.1 1-1 3-1.2.2 4-1.2.1.1.1 5-1.2 5-1.2.3.1 7-1.2.3.r 9-1.2.3 11-1.2.3.1.2.r 12-1.2.3.1.2.1 14-1.2.3.1.2 15-1.2.3.1.2 17-1.2.3.1.2.3.1.1.1.1 20-1.2.3.1.2.1
(o / observe-01~e.1
:ARG0 (w / we~e.0)
:ARG1 (p / phosphorylate-01~e.5
:ARG1 (p2 / protein
:name (n / name :op1 "HSP27"~e.4))
:ARG1-of (u / uniform-02~e.3)
:ARG2-of~e.7 (e / except-01~e.9
:ARG1 (p3 / phosphorylate-01~e.5
:ARG1 p2
:location~e.11 (c / cell-line~e.14,15 :quant 3~e.12,20
:mod (m2 / medical-condition
:name (n2 / name :op1 "melanoma")
:mod (u2 / uveal))
:ARG1-of (m / mean-01
:ARG2 (a / and
:op1 (c2 / cell-line
:name (n3 / name :op1 "OCM1"~e.17))
:op2 (c3 / cell-line
:name (n4 / name :op1 "OCM3"))
:op3 (c4 / cell-line
:name (n5 / name :op1 "OCM8")))))))))
# ::id pmid_1956_8237.96 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok UMs displaying activated ERK1 @/@ 2 as well as phosphorylated HSP27 were most common , whereas signals for phosphorylated ERK1 @/@ 2 were low in metastasis tissue ( MET1 @-@ 3 ) and metastatic UM cell lines ( OMM1 , OMM2.3 and OMM2.5 ) ( Figure 1 ) .
# ::alignments 1-1.1.1.3 2-1.1.1.3.1.1.2 3-1.1.1.3.1.1.1.1 5-1.1.1.3.1.1.1.1 6-1.1.1.3.1 7-1.1.1.3.1 8-1.1.1.3.1 8-1.1.1.3.1.r 9-1.1.1.3.1.2.2 10-1.1.1.3.1.2.1.1 11-1.1.1.r 12-1.1.2 13-1.1 15-1 16-1.2.1 17-1.2.1.1.r 18-1.2.1.1.2 19-1.2.1.1.1.1 21-1.2.1.1.1.1 23-1.2 24-1.2.2.r 25-1.2.2.1.1 26-1.2.2.1 30-1.2.2.1.2.1.2.2 33-1.2.2.1.1 35-1.2.2.2 36-1.2.2.2 38-1.2.2.2.3.1.1.1.1 40-1.2.2.2.3.1.2.1.1 41-1.2.2.2.3.1 42-1.2.2.2.3.1.3.1.1 46-1.3.1 47-1.2.2.1.2.1.2.1 47-1.3.1.1
(c / contrast-01~e.15
:ARG1 (c2 / common~e.13
:domain~e.11 (m4 / medical-condition
:name (n / name :op1 "melanoma")
:mod (u / uveal)
:ARG0-of (d2 / display-01~e.1
:ARG1~e.8 (a / and~e.6,7,8
:op1 (e / enzyme
:name (n2 / name :op1 "ERK1/2"~e.3,5)
:ARG1-of (a2 / activate-01~e.2))
:op2 (p2 / protein
:name (n3 / name :op1 "HSP27"~e.10)
:ARG3-of (p / phosphorylate-01~e.9)))))
:degree (m / most~e.12))
:ARG2 (l / low-04~e.23
:ARG1 (s / signal-07~e.16
:beneficiary~e.17 (e2 / enzyme
:name (n4 / name :op1 "ERK1/2"~e.19,21)
:ARG3-of (p3 / phosphorylate-01~e.18)))
:location~e.24 (a3 / and
:op1 (t / tissue~e.26
:ARG1-of (m2 / metastasize-101~e.25,33)
:ARG1-of (l2 / label-01
:ARG2 (t2 / thing
:name (n5 / name :op1 "MET")
:value (v / value-interval :op1 1~e.47 :op2 3~e.30))))
:op2 (c3 / cell-line~e.35,36
:mod m4
:mod m2
:ARG1-of (m3 / mean-01
:ARG2 (a4 / and~e.41
:op1 (c4 / cell-line
:name (n6 / name :op1 "OMM1"~e.38))
:op2 (c5 / cell-line
:name (n7 / name :op1 "OMM2.3"~e.40))
:op3 (c6 / cell-line
:name (n8 / name :op1 "OMM2.5"~e.42)))))))
:ARG1-of (d3 / describe-01
:ARG0 (f / figure~e.46 :mod 1~e.47)))
# ::id pmid_1956_8237.97 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Remarkably , two of the metastatic cell lines ( OMM2.3 , OMM2.5 ) are derived from the same patient as cell line Mel270 but contained far less activated ERK1 @/@ 2 .
# ::alignments 0-1.3 2-1.1.1.1 5-1.1.1.2.2 6-1.1.1.2.1.1 7-1.1.1.2.1.1 9-1.1.1.2.1.1.1.1 11-1.1.1.2.1.2.1.1 14-1.1 15-1.1.2.r 17-1.1.2 17-1.1.2.2 17-1.1.2.2.r 18-1.1.2.1.1 20-1.1.1 20-1.1.1.3.1 21-1.1.1 21-1.1.1.3.1 22-1.1.3.1.1 23-1 24-1.2 25-1.2.2.3.1 26-1.2.2.3 27-1.2.2.2 28-1.2.2.1.1 30-1.2.2.1.1
(c / contrast-01~e.23
:ARG1 (d / derive-01~e.14
:ARG1 (c2 / cell-line~e.20,21 :quant 2~e.2
:ARG1-of (m2 / mean-01
:ARG2 (a / and
:op1 (c4 / cell-line~e.6,7
:name (n / name :op1 "OMM2.3"~e.9))
:op2 (c5 / cell-line
:name (n2 / name :op1 "OMM2.5"~e.11)))
:ARG1-of (m / metastasize-101~e.5))
:ARG1-of (i / include-91
:ARG2 (c3 / cell-line~e.20,21)))
:ARG2~e.15 (p / person~e.17
:ARG0-of (h / have-rel-role-91
:ARG2 (p2 / patient~e.18))
:ARG1-of~e.17 (s / same-01~e.17))
:ARG4 (c6 / cell-line
:name (n3 / name :op1 "Mel270"~e.22)))
:ARG2 (c7 / contain-01~e.24
:ARG0 c2
:ARG1 (e / enzyme
:name (n4 / name :op1 "ERK1/2"~e.28,30)
:ARG1-of (a2 / activate-01~e.27)
:quant (l / less~e.26
:degree (f / far~e.25))))
:ARG1-of (r / remarkable-02~e.0))
# ::id pmid_1956_8237.98 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Differential kinase activity in UM
# ::alignments 1-1.2 2-1.1 3-1
(a / activity-06~e.3
:ARG0 (k / kinase~e.2)
:mod (d / differential~e.1)
:location (m / medical-condition
:name (n / name :op1 "melanoma")
:mod (u / uveal)))
# ::id pmid_1956_8237.99 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Reduction of ERK1 @/@ 2 activation in metastatic cell lines compared with that in primary UM cell lines provides a model to identify the underlying mechanism of ERK1 @/@ 2 activation in the absence of BRAF and NRAS mutations .
# ::alignments 0-1.1 0-1.1.2.1 1-1.1.1.r 2-1.1.1.1.1.1 4-1.1.1.1.1.1 5-1.1.1 6-1.1.1.2.r 7-1.1.1.2.1 8-1.1.1.2 8-1.1.2.1.2 9-1.1.1.2 10-1.1.2 13-1.1.2.1.2.1.r 14-1.1.2.1.2.1.3 16-1.1.2.1.1 17-1.1.2.1.1 18-1 20-1.2 22-1.2.1 24-1.2.1.1.1 25-1.2.1.1 26-1.2.1.1.2.r 27-1.2.1.1.2.1 28-1.2.1.1.2.1 29-1.2.1.1.2.1 30-1.2.1.1.2 31-1.2.1.1.2.2.r 33-1.2.1.1.2.2 36-1.2.1.1.2.2.1.1.1.1.1 38-1.2.1.1.2.2.1 40-1.2.1.1.2.2.1.2.1.1.1 42-1.2.1.1.2.2.1.1 42-1.2.1.1.2.2.1.2
(p / provide-01~e.18
:ARG0 (r / reduce-01~e.0
:ARG1~e.1 (a / activate-01~e.5
:ARG1 (e / enzyme
:name (n / name :op1 "ERK1/2"~e.2,4))
:location~e.6 (c / cell-line~e.8,9
:ARG1-of (m / metastasize-101~e.7)))
:ARG1-of (c2 / compare-01~e.10
:ARG2 (r2 / reduce-01~e.0
:ARG1 a~e.16,17
:location (c3 / cell-line~e.8
:mod~e.13 (m6 / medical-condition
:name (n2 / name :op1 "melanoma")
:mod (u / uveal)
:mod (p2 / primary~e.14))))))
:ARG1 (m2 / model-01~e.20
:purpose (i / identify-01~e.22
:ARG1 (m3 / mechanism~e.25
:ARG1-of (u2 / underlie-01~e.24)
:mod~e.26 (a2 / activate-01~e.30
:ARG1 e~e.27,28,29
:condition~e.31 (a3 / absent-01~e.33
:ARG1 (a4 / and~e.38
:op1 (m4 / mutate-01~e.42
:ARG1 (g / gene
:name (n3 / name :op1 "BRAF"~e.36)))
:op2 (m5 / mutate-01~e.42
:ARG1 (g2 / gene
:name (n4 / name :op1 "NRAS"~e.40))))))))))
# ::id pmid_1956_8237.100 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To investigate whether a kinase is differentially activated between primary UM cell lines and metastatic UM cell lines , we used peptide @-@ based tyrosine kinase arrays ( Lemeer et al , 2007 ) .
# ::alignments 1-1.3 2-1.3.2.1 2-1.3.2.1.r 4-1.3.2.2 6-1.3.2.3 6-1.3.2.3.r 7-1.3.2 9-1.3.2.4.1.1.3 11-1.3.2.4.1 12-1.3.2.4.1 12-1.3.2.4.2 13-1.3.2.4 14-1.3.2.4.2.1.3 16-1.3.2.4.1 17-1.3.2.4.1 19-1.1 20-1 21-1.2.2.1 23-1.2.2 24-1.2.1.1.1 25-1.2.1.1.2 26-1.2 29-1.2.3.1.1.1.1.1 31-1.2.3.1.1 32-1.2.3.1.1.2.1 35-1.2.3.1.2.1
(u3 / use-01~e.20
:ARG0 (w / we~e.19)
:ARG1 (a3 / array-01~e.26
:ARG1 (e2 / enzyme
:name (n5 / name :op1 "tyrosine"~e.24 :op2 "kinase"~e.25))
:ARG1-of (b / base-02~e.23
:ARG2 (p2 / peptide~e.21))
:ARG1-of (d4 / describe-01
:ARG0 (p3 / publication-91
:ARG0 (a4 / and~e.31
:op1 (p4 / person
:name (n4 / name :op1 "Lemeer"~e.29))
:op2 (p5 / person
:mod (o / other~e.32)))
:time (d5 / date-entity :year 2007~e.35))))
:ARG2 (i / investigate-01~e.1
:ARG0 w
:ARG1 (a / activate-01~e.7 :mode~e.2 interrogative~e.2
:ARG1 (k / kinase~e.4)
:manner~e.6 (d / differential~e.6)
:location (a2 / and~e.13
:op1 (c / cell-line~e.11,12,16,17
:mod (m2 / medical-condition
:name (n / name :op1 "melanoma")
:mod (u / uveal)
:mod (p / primary~e.9)))
:op2 (c2 / cell-line~e.12
:mod (m3 / medical-condition
:name (n2 / name :op1 "melanoma")
:mod u
:ARG1-of (m / metastasize-101~e.14)))))))
# ::id pmid_1956_8237.101 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The UM cell lines displayed a high kinase activity , whereas the metastatic UM cell lines displayed a low kinase activity , although the same amount of lysate was incubated ( Figure 2A ) .
# ::alignments 2-1.1.1.1 3-1.1.1.1 4-1.1.1 6-1.1.1.2.2 7-1.1.1.2.1 8-1.1.1.2 10-1.1 12-1.1.2.1.1.2 14-1.1.1.1 15-1.1.2.1 16-1.1.2 18-1.1.2.2.2 19-1.1.2.2.1 20-1.1.2.2 22-1 24-1.2.1.2 25-1.2.1 26-1.2.1.1.r 27-1.2.1.1 29-1.2 32-1.3.1 33-1.3.1.1
(h2 / have-concession-91~e.22
:ARG1 (c / contrast-01~e.10
:ARG1 (d / display-01~e.4
:ARG0 (c2 / cell-line~e.2,3,14
:mod (m3 / medical-condition
:name (n / name :op1 "melanoma")
:mod (u / uveal)))
:ARG1 (a / activity-06~e.8
:ARG0 (k / kinase~e.7)
:ARG1-of (h / high-02~e.6)))
:ARG2 (d3 / display-01~e.16
:ARG0 (c3 / cell-line~e.15
:mod (m2 / medical-condition
:name (n2 / name :op1 "melanoma")
:ARG1-of (m / metastasize-101~e.12)))
:ARG1 (a2 / activity-06~e.20
:ARG0 k~e.19
:ARG1-of (l / low-04~e.18))))
:ARG2 (i / incubate-01~e.29
:ARG1 (a3 / amount~e.25
:quant-of~e.26 (l2 / lysate~e.27)
:ARG1-of (s / same-01~e.24)))
:ARG1-of (d5 / describe-01
:ARG0 (f / figure~e.32 :mod "2A"~e.33)))
# ::id pmid_1956_8237.102 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok After normalisation , we could analyse the kinase data and identify nine substrates that were significantly differentially phosphorylated between primary and metastatic UM cell lines ( Figure 2B , Table 1 ) .
# ::alignments 0-1.2 3-1.1.1.1 4-1 7-1.1.1.2.1 8-1.1.1.2 9-1.1 10-1.1.2 11-1.1.2.2.1 12-1.1.2.2 15-1.1.2.2.2.1 16-1.1.2.2.2.2 16-1.1.2.2.2.2.r 17-1.1.2.2.2 19-1.1.2.2.2.3.1.1.3 20-1.1.2.2.2.3 21-1.1.2.2.2.3.2.1.3 23-1.1.2.2.2.3.1 23-1.1.2.2.2.3.2 24-1.1.2.2.2.3.1 27-1.3.1.1 28-1.3.1.1.1 32-1.3.1.2 33-1.3.1.2.1
(p / possible-01~e.4
:ARG1 (a / and~e.9
:op1 (a2 / analyze-01
:ARG0 (w / we~e.3)
:ARG1 (d / data~e.8
:topic (k / kinase~e.7)))
:op2 (i / identify-01~e.10
:ARG0 w
:ARG1 (s / substrate~e.12 :quant 9~e.11
:ARG3-of (p2 / phosphorylate-01~e.17
:ARG1-of (s2 / significant-02~e.15)
:manner~e.16 (d2 / differential~e.16)
:location (a3 / and~e.20
:op1 (c / cell-line~e.23,24
:mod (m2 / medical-condition
:name (n / name :op1 "melanoma")
:mod (u / uveal)
:mod (p3 / primary~e.19)))
:op2 (c2 / cell-line~e.23
:mod (m3 / medical-condition
:name (n2 / name :op1 "melanoma")
:mod (u2 / uveal)
:ARG1-of (m / metastasize-101~e.21))))))))
:time (a4 / after~e.0
:op1 (n3 / normalize-01))
:ARG1-of (d5 / describe-01
:ARG0 (a5 / and
:op1 (f / figure~e.27 :mod "2B"~e.28)
:op2 (t / table~e.32 :mod 1~e.33))))
# ::id pmid_1956_8237.103 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Primary UM and metastatic tissue also showed differential phosphorylation of these nine peptides , although not as clearly as observed in the cell lines ( Figure 2C ) .
# ::alignments 0-1.1.1.3 2-1.1 3-1.1.2.1 4-1.1.2 5-1.4 6-1 7-1.2.2 8-1.2 8-1.3.3 9-1.2.1.r 10-1.2.1.2 11-1.2.1.1 12-1.2.1 14-1.3.r 15-1.3.1 15-1.3.1.r 17-1.3 18-1.3.3.1.r 19-1.3.3.1 20-1.3.3.1.1.r 22-1.3.3.1.1 23-1.3.3.1.1 26-1.5.1 27-1.5.1.1
(s / show-01~e.6
:ARG0 (a / and~e.2
:op1 (m2 / medical-condition
:name (n / name :op1 "melanoma")
:mod (u / uveal)
:mod (p / primary~e.0))
:op2 (t / tissue~e.4
:ARG1-of (m / metastasize-101~e.3)))
:ARG1 (p2 / phosphorylate-01~e.8
:ARG1~e.9 (p3 / peptide~e.12 :quant 9~e.11
:mod (t2 / this~e.10))
:mod (d2 / differential~e.7))
:concession~e.14 (c / clear-06~e.17 :polarity~e.15 -~e.15
:ARG1 s
:compared-to (p4 / phosphorylate-01~e.8
:ARG1-of~e.18 (o / observe-01~e.19
:location~e.20 (c2 / cell-line~e.22,23))))
:mod (a2 / also~e.5)
:ARG1-of (d3 / describe-01
:ARG0 (f / figure~e.26 :mod "2C"~e.27)))
# ::id pmid_1956_8237.104 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Candidate kinase : Src
# ::alignments 1-1.1.2 2-1.1 4-1.1.1.1
(p / protein
:domain (k / kinase~e.2
:name (n / name :op1 "Src"~e.4)
:mod (c / candidate~e.1)))
# ::id pmid_1956_8237.105 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We identified nine peptides derived from eight proteins that were differentially phosphorylated between primary and metastatic cell line lysates .
# ::alignments 0-1.1 1-1 2-1.2.1 3-1.2 4-1.2.2 5-1.2.2.1.r 6-1.2.2.1.1 7-1.2.2.1 10-1.2.2.1.2.1 10-1.2.2.1.2.1.r 11-1.2.2.1.2 13-1.2.2.1.2.2.1.2 14-1.2.2.1.2.2 15-1.2.2.1.2.2.2.2 16-1.2.2.1.2.2.1.1 17-1.2.2.1.2.2.1.1 17-1.2.2.1.2.2.2.1 18-1.2.2.1.2.2.1 18-1.2.2.1.2.2.2
(i / identify-01~e.1
:ARG0 (w / we~e.0)
:ARG1 (p / peptide~e.3 :quant 9~e.2
:ARG1-of (d / derive-01~e.4
:ARG2~e.5 (p2 / protein~e.7 :quant 8~e.6
:ARG3-of (p3 / phosphorylate-01~e.11
:manner~e.10 (d2 / differential~e.10)
:location (a / and~e.14
:op1 (l / lysate~e.18
:mod (c / cell-line~e.16,17)
:mod (p4 / primary~e.13))
:op2 (l2 / lysate~e.18
:mod (c2 / cell-line~e.17)
:ARG1-of (m / metastasize-101~e.15))))))))
# ::id pmid_1956_8237.106 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok On the basis of a literature search , we identified candidate tyrosine kinases for eight out of nine peptides ( Table 1 ) ( Cooper et al , 1983 ; Thomas and Brugge , 1997 ; Koike et al , 2003 ; Diella et al , 2004 ) .
# ::alignments 2-1.5 3-1.5.1.r 5-1.5.1.1 6-1.5.1 8-1.1 9-1 10-1.2.2 11-1.2.1.1 12-1.2.1.2 13-1.3.r 14-1.3.1 17-1.3.2.1.1 18-1.3 18-1.3.2.1 21-1.4.1 22-1.4.1.1 27-1.5.1.1.1.1.1.1.1.1.1 29-1.5.1.1.1.1.1.1 30-1.5.1.1.1.1.1.1.2.1 33-1.5.1.1.1.1.1.2.1 37-1.5.1.1.1.1.2.1.1.1.1 38-1.5.1.1.1.1.2.1 39-1.5.1.1.1.1.2.1.2.1.1 41-1.5.1.1.1.1.2.2.1 45-1.5.1.1.1.1.3.1.1.1.1 47-1.5.1.1.1.1.3.1 48-1.5.1.1.1.1.3.1.2.1 51-1.5.1.1.1.1.3.2.1 55-1.5.1.1.1.1.4.1.1.1.1 57-1.5.1.1.1.1 57-1.5.1.1.1.1.4.1 58-1.5.1.1.1.1.4.1.2.1 61-1.5.1.1.1.1.4.2.1
(i / identify-01~e.9
:ARG0 (w / we~e.8)
:ARG1 (e / enzyme
:name (n7 / name :op1 "tyrosine"~e.11 :op2 "kinase"~e.12)
:mod (c / candidate~e.10))
:beneficiary~e.13 (p / peptide~e.18 :quant 8~e.14
:ARG1-of (i2 / include-91
:ARG2 (p2 / peptide~e.18 :quant 9~e.17)))
:ARG1-of (d5 / describe-01
:ARG0 (t / table~e.21 :mod 1~e.22))
:ARG1-of (b / base-02~e.2
:ARG2~e.3 (s / search-01~e.6
:ARG1 (l / literature~e.5
:ARG2-of (i3 / include-91
:ARG1 (a / and~e.57
:op1 (p3 / publication-91
:ARG0 (a2 / and~e.29
:op1 (p4 / person
:name (n2 / name :op1 "Cooper"~e.27))
:op2 (p5 / person
:mod (o / other~e.30)))
:time (d / date-entity :year 1983~e.33))
:op2 (p6 / publication-91
:ARG0 (a3 / and~e.38
:op1 (p7 / person
:name (n3 / name :op1 "Thomas"~e.37))
:op2 (p8 / person
:name (n4 / name :op1 "Brugge"~e.39)))
:time (d2 / date-entity :year 1997~e.41))
:op3 (p9 / publication-91
:ARG0 (a4 / and~e.47
:op1 (p10 / person
:name (n5 / name :op1 "Koike"~e.45))
:op2 (p11 / person
:mod (o2 / other~e.48)))
:time (d3 / date-entity :year 2003~e.51))
:op4 (p12 / publication-91
:ARG0 (a5 / and~e.57
:op1 (p13 / person
:name (n6 / name :op1 "Diella"~e.55))
:op2 (p14 / person
:mod (o3 / other~e.58)))
:time (d4 / date-entity :year 2004~e.61))))))))
# ::id pmid_1956_8237.107 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Among the candidates , Src and Src family members were most prominent .
# ::alignments 0-1.1.2.1 0-1.1.3 2-1.1.3.1 4-1.1.1.1.1 4-1.1.2.1.1.1.1 5-1.1 6-1.1.1.1.1 6-1.1.2.1.1.1.1 7-1.1.2.1.1 8-1.1.2 9-1.1.r 10-1.2 11-1
(p / prominent~e.11
:domain~e.9 (a / and~e.5
:op1 (p2 / protein
:name (n / name :op1 "Src"~e.4,6))
:op2 (m / member~e.8
:ARG1-of (i2 / include-91~e.0
:ARG2 (p3 / protein-family~e.7
:name (n2 / name :op1 "Src"~e.4,6))))
:ARG1-of (i / include-91~e.0
:ARG2 (c / candidate~e.2)))
:degree (m2 / most~e.10))
# ::id pmid_1956_8237.108 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To validate the candidacy of Src , we performed in vitro inhibition experiments with the Src @-@ kinase @-@ specific inhibitors PP1 and the PP1 analogue , PP2 .
# ::alignments 1-1.3 3-1.3.2 4-1.3.2.1.r 5-1.3.2.1 7-1.1 8-1 10-1.2.3 11-1.2.3 13-1.2.1 13-1.2.2 13-1.2.2.1 13-1.2.2.1.r 14-1.2 17-1.2.2.2.1.1.1 19-1.2.2.2.1 21-1.2.2.2 22-1.2.2 22-1.2.2.1 22-1.2.2.1.r 23-1.2.2.3.1.1.1.1 26-1.2.2.3.1.1.1.1 27-1.2.2.3.1.2.2 29-1.2.2.3.1.2.1.1
(p / perform-02~e.8
:ARG0 (w / we~e.7)
:ARG1 (e / experiment-01~e.14
:ARG1 (i / inhibit-01~e.13)
:ARG2 (s / small-molecule~e.13,22
:ARG0-of~e.13,22 (i3 / inhibit-01~e.13,22)
:ARG1-of (s2 / specific-02~e.21
:ARG2 (k / kinase~e.19
:name (n / name :op1 "Src"~e.17)))
:ARG1-of (m / mean-01
:ARG2 (a / and
:op1 (p2 / protein
:name (n2 / name :op1 "PP1"~e.23,26))
:op2 (p3 / protein
:name (n3 / name :op1 "PP2"~e.29)
:mod (a2 / analogue~e.27
:mod p2)))))
:manner (i2 / in-vitro~e.10,11))
:purpose (v / validate-01~e.1
:ARG0 w
:ARG1 (c / candidacy~e.3
:mod~e.4 k~e.5)))
# ::id pmid_1956_8237.109 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We added PP1 and PP2 ( 10 μ @ M ) to lysates of primary UM tissue and of a primary UM cell line and measured the inhibitory effect of these Src inhibitors using kinase array ( Figure 3A ) .
# ::alignments 0-1.1.1 1-1.1 3-1.1.2 3-1.1.3 6-1.1.2.3.1 15-1.1.3.1 15-1.1.3.2 16-1.1.3.1.1.r 17-1.1.3.1.1.1.3 19-1.1.3.1.1 23-1.1.3.1.1.1.3 25-1.1.3.2.1 26-1.1.3.2.1 27-1 28-1.2 30-1.2.2.1 30-1.2.2.1.1 30-1.2.2.1.1.r 30-1.2.2.2 31-1.2.2 34-1.2.2.1.1.1.1.1 35-1.2.2.1 35-1.2.2.1.1 35-1.2.2.1.1.r 35-1.2.2.2 37-1.2.3.1 38-1.2.3 41-1.3.1 42-1.3.1.1
(a / and~e.27
:op1 (a2 / add-02~e.1
:ARG0 (w / we~e.0)
:ARG1 (a3 / and~e.3
:op1 (s / small-molecule)
:op2 (s2 / small-molecule)
:quant (c2 / concentration-quantity :quant 10~e.6
:unit (m / micromolar)))
:ARG2 (a7 / and~e.3
:op1 (l / lysate~e.15
:source~e.16 (t / tissue~e.19
:mod (m3 / medical-condition
:name (n3 / name :op1 "melanoma")
:mod (u / uveal)
:mod (p / primary~e.17,23))))
:op1 (l2 / lysate~e.15
:source (c / cell-line~e.25,26
:mod m3))))
:op2 (m2 / measure-01~e.28
:ARG0 w
:ARG1 (a5 / affect-01~e.31
:ARG0 (s3 / small-molecule~e.30,35
:ARG0-of~e.30,35 (i2 / inhibit-01~e.30,35
:ARG1 (p2 / protein-family
:name (n4 / name :op1 "Src"~e.34))))
:ARG2 (i / inhibit-01~e.30,35))
:instrument (a6 / array-01~e.38
:ARG1 (k / kinase~e.37)))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.41 :mod "3A"~e.42)))
# ::id pmid_1956_8237.110 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok A total of seven out of nine substrates that identified Src in the first screen displayed a significantly reduced phosphorylation when PP1 or PP2 were added to lysates of UM1 and Mel270 ( Figure 3A ) .
# ::alignments 1-1.1.3 3-1.1.1 6-1.1.2.1.1 7-1.1 7-1.1.2.1 9-1.1.2.1.2 10-1.1.2.1.2.1.1.1 11-1.1.2.1.2.2.r 13-1.1.2.1.2.2.1 13-1.1.2.1.2.2.1.1 13-1.1.2.1.2.2.1.1.r 14-1.1.2.1.2.2 15-1 17-1.2.1.1 18-1.2.1 19-1.2 20-1.3.r 21-1.3.1.1.1.1 22-1.3.1 23-1.3.1.2.1.1 25-1.3 26-1.3.2.r 27-1.3.2.1 27-1.3.2.2 28-1.3.2.1.1.r 29-1.3.2.1.1.1.1 30-1.3.2 31-1.3.2.2.1.1.1 34-1.4.1 35-1.4.1.1
(d / display-01~e.15
:ARG0 (s / substrate~e.7 :quant 7~e.3
:ARG1-of (i2 / include-91
:ARG2 (s3 / substrate~e.7 :quant 9~e.6
:ARG0-of (i / identify-01~e.9
:ARG1 (p / protein
:name (n / name :op1 "Src"~e.10))
:location~e.11 (s2 / screen~e.14
:ord (o / ordinal-entity~e.13 :value~e.13 1~e.13)))))
:ARG1-of (t / total-01~e.1))
:ARG1 (p2 / phosphorylate-01~e.19
:ARG1-of (r / reduce-01~e.18
:ARG2 (s4 / significant-02~e.17)))
:time~e.20 (a / add-02~e.25
:ARG1 (o2 / or~e.22
:op1 (p3 / protein
:name (n2 / name :op1 "PP1"~e.21))
:op2 (p4 / protein
:name (n3 / name :op1 "PP2"~e.23)))
:ARG2~e.26 (a3 / and~e.30
:op1 (l / lysate~e.27
:source~e.28 (t2 / thing
:name (n4 / name :op1 "UM1"~e.29)))
:op2 (l2 / lysate~e.27
:source (c / cell-line
:name (n5 / name :op1 "Mel270"~e.31)))))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.34 :mod "3A"~e.35)))
# ::id pmid_1956_8237.111 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The PLCG1 peptide and one of the PAX1 ( Y31 ) substrates did not reach significance but were still phosphorylated at a reduced level after PP1 and PP2 treatments .
# ::alignments 1-1.1.2.1.1.1 2-1.1.2.1 3-1.1.2 7-1.1.2.2.2.1.1.1 9-1.1.2.2.1.1 11-1.1.2.2 11-1.1.2.2.2.1 13-1.1.1 13-1.1.1.r 14-1.1 15-1.1.3 16-1 18-1.2.4 19-1.2 20-1.2.2.r 22-1.2.2.1 23-1.2.2 24-1.2.3 25-1.2.3.1.1.1.1.1 26-1.2.3.1.1 27-1.2.3.1.1.2.1.1 28-1.2.3.1
(c / contrast-01~e.16
:ARG1 (r / reach-01~e.14 :polarity~e.13 -~e.13
:ARG0 (a / and~e.3
:op1 (p / peptide~e.2
:name (n / name :op1 "PLCG1"~e.1))
:op1 (s / substrate~e.11
:name (n2 / name :op1 "Y31"~e.9)
:ARG1-of (i / include-91
:ARG2 (s2 / substrate~e.11
:name (n3 / name :op1 "PAX1"~e.7)))))
:ARG1 (s3 / significance~e.15))
:ARG2 (p2 / phosphorylate-01~e.19
:ARG1 a
:degree~e.20 (l / level~e.23
:ARG1-of (r2 / reduce-01~e.22))
:time (a2 / after~e.24
:op1 (t / treat-04~e.28
:ARG2 (a3 / and~e.26
:op1 (p3 / protein
:name (n4 / name :op1 "PP1"~e.25))
:op2 (p4 / protein
:name (n5 / name :op1 "PP2"~e.27)))))
:mod (s6 / still~e.18)))
# ::id pmid_1956_8237.112 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The peptide representing FAK1 Y576 @/@ Y577 is a genuine substrate for Src , which was not detected in the UM cell line comparison , but phosphorylation was significantly downregulated by PP1 and PP2 treatments .
# ::alignments 1-1.1.2 2-1.1.2.1 7-1.1.2.r 9-1.1.1 10-1.1 11-1.1.3.r 12-1.1.3.1.1 15-1.1.2.r 16-1.1.4.1 16-1.1.4.1.r 17-1.1.4 21-1.1.4.2.1 22-1.1.4.2.1 23-1.1.4.2 25-1 26-1.2.1 28-1.2.3 29-1.2 30-1.2.2.r 31-1.2.2.1.1.1.1 32-1.2.2.1 33-1.2.2.1.2.1.1 34-1.2.2
(c / contrast-01~e.25
:ARG1 (s / substrate~e.10
:mod (g / genuine~e.9)
:domain~e.7,15 (p / peptide~e.1
:ARG0-of (r / represent-01~e.2
:ARG1 (o / or
:op1 (a / amino-acid :mod 576
:name (n / name :op1 "tyrosine"))
:op2 (a2 / amino-acid :mod 577
:name (n2 / name :op1 "tyrosine"))
:part-of (e / enzyme :mod 1
:name (n3 / name :op1 "FAK")))))
:beneficiary~e.11 (p2 / protein
:name (n4 / name :op1 "Src"~e.12))
:ARG1-of (d / detect-01~e.17 :polarity~e.16 -~e.16
:time (c2 / compare-01~e.23
:ARG1 (c3 / cell-line~e.21,22
:mod (m / medical-condition
:name (n5 / name :op1 "melanoma")
:mod (u / uveal))))))
:ARG2 (d3 / downregulate-01~e.29
:ARG1 (p3 / phosphorylate-01~e.26)
:ARG2~e.30 (t / treat-04~e.34
:ARG2 (a3 / and~e.32
:op1 (p4 / protein
:name (n6 / name :op1 "PP1"~e.31))
:op2 (p5 / protein
:name (n7 / name :op1 "PP2"~e.33))))
:ARG1-of (s4 / significant-02~e.28)))
# ::id pmid_1956_8237.113 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In the control experiment , in which we added the inactive analogue of PP1 ( PP3 ) to cell lysates , we did not observe a loss of kinase activity ( not shown ) .
# ::alignments 2-1.4.1 3-1.4 7-1.4.2.1 8-1.4.2 10-1.4.2.2.2 10-1.4.2.2.2.1 10-1.4.2.2.2.1.r 11-1.4.2.2 12-1.4.2.2.3.r 13-1.4.2.2.3.1.1 15-1.4.2.2.1.1 17-1.4.2.3.r 18-1.4.2.3.1 19-1.4.2.3 21-1.4.2.1 23-1.1 23-1.1.r 24-1 26-1.3 27-1.3.1.r 28-1.3.1.1 29-1.3.1 31-1.3.2.1 31-1.3.2.1.r 32-1.3.2
(o / observe-01~e.24 :polarity~e.23 -~e.23
:ARG0 (w / we)
:ARG1 (l / lose-02~e.26
:ARG1~e.27 (a / activity-06~e.29
:ARG0 (k / kinase~e.28))
:ARG1-of (s2 / show-01~e.32 :polarity~e.31 -~e.31))
:location (e / experiment-01~e.3
:mod (c / control~e.2)
:location-of (a2 / add-02~e.8
:ARG0 w~e.7,21
:ARG1 (a3 / analogue~e.11
:name (n2 / name :op1 "PP3"~e.15)
:ARG0-of (a4 / activity-06~e.10 :polarity~e.10 -~e.10)
:poss~e.12 (p / protein
:name (n / name :op1 "PP1"~e.13)))
:ARG2~e.17 (l2 / lysate~e.19
:mod (c2 / cell~e.18)))))
# ::id pmid_1956_8237.114 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The kinase activity of metastasis tissue and UM tissue differed marginally ( Figure 2C ) , and incubation with PP1 ( 10 μ @ M ) resulted in a decimation of kinase activity similar to the inhibition that we observed in UM tissue ( Figure 3B ) .
# ::alignments 1-1.1.3.1 2-1.1.3 4-1.1.2.1 5-1.1.2 8-1.1.1 8-1.1.2 9-1.1 10-1.1.4 13-1.1.5.1 14-1.1.5.1.1 18-1 19-1.2.1 23-1.2.1.1.1.1 31-1.2 32-1.2.2.r 34-1.2.2 35-1.2.2.1.r 36-1.2.2.1.1 37-1.2.2.1 38-1.2.2.1.2 39-1.2.2.1.2.1.r 41-1.2.2.1.2.1 43-1.2.2.1.2.1.1.1 44-1.2.2.1.2.1.1 47-1.1.1 50-1.2.3.1 51-1.2.3.1.1
(a / and~e.18
:op1 (d / differ-02~e.9
:ARG1 (t2 / tissue~e.8,47
:mod (m4 / medical-condition
:name (n / name :op1 "melanoma")
:mod (u / uveal)))
:ARG2 (t / tissue~e.5,8
:ARG1-of (m / metastasize-101~e.4))
:ARG3 (a2 / activity-06~e.2
:mod (k / kinase~e.1))
:ARG1-of (m2 / marginal-02~e.10)
:ARG1-of (d3 / describe-01
:ARG0 (f / figure~e.13 :mod "2C"~e.14)))
:op2 (r / result-01~e.31
:ARG1 (i / incubate-01~e.19
:ARG2 (s / small-molecule
:quant (c / concentration-quantity :quant 10~e.23
:unit (m3 / micromolar))))
:ARG2~e.32 (d4 / decimate-01~e.34
:ARG1~e.35 (a4 / activity-06~e.37
:mod (k2 / kinase~e.36)
:ARG1-of (r2 / resemble-01~e.38
:ARG2~e.39 (i2 / inhibit-01~e.41
:ARG1-of (o / observe-01~e.44
:ARG0 (w / we~e.43)
:location t2)))))
:ARG1-of (d5 / describe-01
:ARG0 (f2 / figure~e.50 :mod "3B"~e.51))))
# ::id pmid_1956_8237.115 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To validate Src activity , Mel270 was transfected with two siRNA constructs that target Src and reduced kinase activity ( Figure 3B ) .
# ::alignments 1-1.3 2-1.3.1.1 3-1.3.1 5-1.1.1.1.1 7-1.1 8-1.1.2.r 9-1.1.2.1 10-1.1.2.2.1.1 11-1.1.2 13-1.1.2.3 14-1.1.2.3.1.1.1 15-1 16-1.2 17-1.2.1.1 18-1.2.1 21-1.4.1 22-1.4.1.1
(a / and~e.15
:op1 (t / transfect-01~e.7
:ARG1 (c / cell-line
:name (n / name :op1 "Mel270"~e.5))
:ARG2~e.8 (c2 / construct~e.11 :quant 2~e.9
:mod (n4 / nucleic-acid
:name (n2 / name :op1 "siRNA"~e.10))
:ARG0-of (t2 / target-01~e.13
:ARG1 (p / protein
:name (n3 / name :op1 "Src"~e.14)))))
:op2 (r2 / reduce-01~e.16
:ARG1 (a2 / activity-06~e.18
:mod (k / kinase~e.17)))
:purpose (v / validate-01~e.1
:ARG1 (a3 / activity-06~e.3
:ARG0 p~e.2))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.21 :mod "3B"~e.22)))
# ::id pmid_1956_8237.116 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Regulation of ERK1 @/@ 2 and growth
# ::alignments 1-1.1 2-1.1.1.r 3-1.1.1.1.1 5-1.1.1.1.1 6-1 7-1.2
(a / and~e.6
:op1 (r / regulate-01~e.1
:ARG1~e.2 (e / enzyme
:name (n / name :op1 "ERK1/2"~e.3,5)))
:op2 (g / grow-01~e.7))
# ::id pmid_1956_8237.117 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To investigate whether Src contributes to ERK1 @/@ 2 activation in Mel270 , we analysed the two Src siRNA @-@ transfected cell cultures with the MAPK antibody array .
# ::alignments 1-1.4 2-1.4.2.1 2-1.4.2.1.r 3-1.4.2.2 4-1.4.2 5-1.4.2.3.r 6-1.4.2.3.1.1.1 8-1.4.2.3.1.1.1 9-1.4.2.3 10-1.4.2.3.2.r 11-1.4.2.3.2.1.1 13-1.1 14-1 16-1.2.1 17-1.2.4.1.1 18-1.2.3.1.1.1 20-1.2.3 21-1.2.2 22-1.2 23-1.3.r 25-1.3.1.1.1.1.1 26-1.3.1 27-1.3
(a / analyze-01~e.14
:ARG0 (w / we~e.13)
:ARG1 (c / culture~e.22 :quant 2~e.16
:mod (c2 / cell~e.21)
:ARG1-of (t / transfect-01~e.20
:ARG2 (n6 / nucleic-acid
:name (n / name :op1 "siRNA"~e.18)))
:mod (p2 / protein
:name (n3 / name :op1 "Src"~e.17)))
:instrument~e.23 (a2 / array-01~e.27
:ARG1 (a3 / antibody~e.26
:ARG0-of (c5 / counter-01
:ARG1 (e2 / enzyme
:name (n2 / name :op1 "MAPK"~e.25)))))
:purpose (i / investigate-01~e.1
:ARG0 w
:ARG1 (c3 / contribute-01~e.4 :mode~e.2 interrogative~e.2
:ARG0 p2~e.3
:ARG1~e.5 (a4 / activate-01~e.9
:ARG1 (e / enzyme
:name (n4 / name :op1 "ERK1/2"~e.6,8))
:location~e.10 (c4 / cell-line
:name (n5 / name :op1 "Mel270"~e.11))))))
# ::id pmid_1956_8237.118 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok At 24 and 48 h after transfection with Src siRNA , we observed a reduced ERK1 phosphorylation , whereas ERK2 phosphorylation was minimally affected ( Figure 4 ) .
# ::alignments 1-1.3.2.1.1 2-1.3.2 3-1.3.2.2.1 4-1.3.2.1.2 4-1.3.2.2.2 5-1.3 6-1.3.1 7-1.3.1.1.r 8-1.3.1.1.2.1.1 9-1.3.1.1.1.1 11-1.1.1 12-1.1 14-1.1.2.2 15-1.1.2.1.1.1 16-1.1.2 18-1 19-1.2.1.1.1.1 20-1.2.1 22-1.2.2 23-1.2 26-1.4.1 27-1.4.1.1
(c / contrast-01~e.18
:ARG1 (o / observe-01~e.12
:ARG0 (w / we~e.11)
:ARG1 (p / phosphorylate-01~e.16
:ARG1 (e / enzyme
:name (n / name :op1 "ERK1"~e.15))
:ARG1-of (r / reduce-01~e.14)))
:ARG2 (a / affect-01~e.23
:ARG1 (p2 / phosphorylate-01~e.20
:ARG1 (e2 / enzyme
:name (n2 / name :op1 "ERK2"~e.19)))
:ARG1-of (m / minimal-02~e.22))
:time (a2 / after~e.5
:op1 (t / transfect-01~e.6
:ARG2~e.7 (n5 / nucleic-acid
:name (n3 / name :op1 "siRNA"~e.9)
:mod (p3 / protein
:name (n4 / name :op1 "Src"~e.8))))
:quant (a3 / and~e.2
:op1 (t2 / temporal-quantity :quant 24~e.1
:unit (h / hour~e.4))
:op2 (t3 / temporal-quantity :quant 48~e.3
:unit (h2 / hour~e.4))))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.26 :mod 4~e.27)))
# ::id pmid_1956_8237.119 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Whether Src inhibition and consequently a lowered ERK activation in UM cell lines is associated with a reduced growth was investigated with the WST @-@ 1 viability assay ( Figure 5 ) .
# ::alignments 0-1.1.1 0-1.1.1.r 1-1.1.2.1.1.1.1 2-1.1.2.1 3-1.1.2 4-1.1.2.2.4 4-1.1.2.2.4.r 6-1.1.2.2.2 7-1.1.2.2.1.1.1 8-1.1.2.2 11-1.1.2.2.3 12-1.1.2.2.3 14-1.1 15-1.1.3.r 15-1.3.r 17-1.1.3.1 18-1.1.3 20-1 21-1.3.r 23-1.3.2.1.1 25-1.3.2.1.1 27-1.3 30-1.2.1 31-1.2.1.1
(i / investigate-01~e.20
:ARG1 (a / associate-01~e.14 :mode~e.0 interrogative~e.0
:ARG1 (a2 / and~e.3
:op1 (i2 / inhibit-01~e.2
:ARG1 (p / protein
:name (n / name :op1 "Src"~e.1)))
:op2 (a3 / activate-01~e.8
:ARG1 (e / enzyme
:name (n2 / name :op1 "ERK"~e.7))
:ARG1-of (l / lower-05~e.6)
:location (c / cell-line~e.11,12
:mod (m / medical-condition
:name (n3 / name :op1 "melanoma")
:mod (u / uveal)))
:manner~e.4 (c2 / consequent~e.4)))
:ARG2~e.15 (g / grow-01~e.18
:ARG1-of (r / reduce-01~e.17)))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.30 :mod 5~e.31))
:instrument~e.15,21 (a4 / assay-01~e.27
:mod (v / viable)
:mod (t / thing
:name (n4 / name :op1 "WST-1"~e.23,25))))
# ::id pmid_1956_8237.120 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok All UM cell lines showed a PP1 @-@ dose and time ( 1 @–@ 6 days ) - dependent reduction in cell viability but the magnitude of the response differed widely .
# ::alignments 0-1.1.1.2 2-1.1.1 3-1.1.1 4-1.1 6-1.1.2.2.1.1.1.1.1 8-1.1.2.2.1.1 9-1.1.2.2.1 10-1.1.2.2.1.2 10-1.1.2.2.1.2.1.1 10-1.1.2.2.1.2.1.2 12-1.1.2.2.1.2.1.1.1 14-1.1.2.2.1.2.1.2.1 15-1.1.2.2.1.2.1.1.2 18-1.1.2.2 19-1.1.2 21-1.1.1 21-1.1.2.1.1 23-1 25-1.2.1 26-1.2.1.1.r 28-1.2.1.1 29-1.2 30-1.2.2
(c / contrast-01~e.23
:ARG1 (s / show-01~e.4
:ARG0 (c2 / cell-line~e.2,3,21
:mod (m2 / medical-condition
:name (n / name :op1 "melanoma")
:mod (u / uveal))
:mod (a / all~e.0))
:ARG1 (r / reduce-01~e.19
:ARG1 (v / viable
:mod (c3 / cell~e.21))
:ARG0-of (d3 / depend-01~e.18
:ARG1 (a2 / and~e.9
:op1 (d4 / dose-01~e.8
:ARG2 (p / protein
:name (n2 / name :op1 "PP1"~e.6)))
:op2 (t / time~e.10
:quant (b / between
:op1 (t2 / temporal-quantity~e.10 :quant 1~e.12
:unit (d5 / day~e.15))
:op2 (t3 / temporal-quantity~e.10 :quant 6~e.14
:unit d5)))))))
:ARG2 (d2 / differ-02~e.29
:ARG1 (m / magnitude~e.25
:mod~e.26 (r2 / respond-01~e.28))
:ARG2-of (w / wide-02~e.30)))
# ::id pmid_1956_8237.121 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In general , the metastatic UM cell lines were less affected by PP1 .
# ::alignments 1-1.4 4-1.2.1.3 6-1.2 7-1.2 9-1.3 10-1 11-1.1.r 12-1.1.1.1
(a / affect-01~e.10
:ARG0~e.11 (p / protein
:name (n2 / name :op1 "PP1"~e.12))
:ARG1 (c / cell-line~e.6,7
:mod (m2 / medical-condition
:name (n / name :op1 "melanoma")
:mod (u / uveal)
:ARG1-of (m / metastasize-101~e.4)))
:degree (l / less~e.9)
:ARG1-of (g / general-02~e.1))
# ::id pmid_1956_8237.122 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We also determined the growth inhibition rate of PP1 in cultures of five primary UM cell cultures and observed an increased sensitivity to PP1 treatment compared with the cell lines .
# ::alignments 0-1.1.1 1-1.1.3 2-1.1 4-1.1.2.1.2 5-1.1.2.1 6-1.1.2 7-1.1.2.1.1.r 8-1.1.2.1.1.1.1 9-1.1.2.2.r 10-1.1.2.2 10-1.1.2.2.1.1 12-1.1.2.2.1.1.1 13-1.1.2.2.1.1.3.3 15-1.1.2.2.1.1.2 16-1.1.2.2.1.1 17-1 18-1.2 20-1.2.2.2 21-1.2.2 22-1.2.2.1.r 23-1.2.2.1.1 24-1.2.2.1 25-1.2.2.3.r 28-1.2.2.3 29-1.2.2.3
(a / and~e.17
:op1 (d / determine-01~e.2
:ARG0 (w / we~e.0)
:ARG1 (r / rate~e.6
:degree-of (i / inhibit-01~e.5
:ARG0~e.7 (p2 / protein
:name (n / name :op1 "PP1"~e.8))
:ARG1 (g / grow-01~e.4))
:location~e.9 (c / culture~e.10
:ARG1-of (i2 / include-91
:ARG2 (c2 / culture~e.10,16 :quant 5~e.12
:mod (c3 / cell~e.15)
:mod (m / medical-condition
:name (n2 / name :op1 "melanoma")
:mod (u / uveal)
:mod (p / primary~e.13))))))
:mod (a2 / also~e.1))
:op2 (o / observe-01~e.18
:ARG0 w
:ARG1 (s2 / sensitive-03~e.21
:ARG1~e.22 (t / treat-04~e.24
:ARG2 p2~e.23)
:ARG1-of (i3 / increase-01~e.20)
:compared-to~e.25 (c4 / cell-line~e.28,29))))
# ::id pmid_1956_8237.123 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We had to take samples at day 3 of PP1 treatment because , thereafter , massive cell death occurred ( Figure 5B ) .
# ::alignments 0-1.1 1-1 2-1 2-1.3 2-1.3.r 3-1.2 4-1.2.2 4-1.2.2.1 4-1.2.2.1.r 6-1.2.3.2.2 7-1.2.3.2.1 9-1.2.3.1.1.1.1 10-1.2.3.1 11-1.3 15-1.3.1.2 16-1.3.1.1 17-1.3.1 21-1.4.1 22-1.4.1.1
(o / obligate-01~e.1,2
:ARG1 (w / we~e.0)
:ARG2 (t / take-01~e.3
:ARG0 w
:ARG1 (t4 / thing~e.4
:ARG1-of~e.4 (s / sample-01~e.4))
:time (a / after
:op1 (t2 / treat-04~e.10
:ARG2 (p / protein
:name (n / name :op1 "PP1"~e.9)))
:quant (t3 / temporal-quantity :quant 3~e.7
:unit (d / day~e.6))))
:ARG1-of~e.2 (c / cause-01~e.2,11
:ARG0 (d2 / die-01~e.17
:ARG1 (c2 / cell~e.16)
:mod (m / massive~e.15)
:time (a2 / after
:op1 a)))
:ARG1-of (d3 / describe-01
:ARG0 (f / figure~e.21 :mod "5B"~e.22)))
# ::id pmid_1956_8237.124 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Src protein is reduced in metastasis cell line
# ::alignments 1-1.1.1.1 2-1.1 4-1 5-1.2.r 6-1.2.1 7-1.2 8-1.2
(r / reduce-01~e.4
:ARG1 (p / protein~e.2
:name (n / name :op1 "Src"~e.1))
:location~e.5 (c / cell-line~e.7,8
:ARG1-of (m / metastasize-101~e.6)))
# ::id pmid_1956_8237.125 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Src is regulated by the phosphorylation of tyrosine residues at position 416 ( Y416 ) and 527 ( Y527 ) .
# ::alignments 0-1.2.1.1 2-1 3-1.1.r 5-1.1 6-1.1.1.r 7-1.1.1.1.1.2.1 7-1.1.1.2.1.2.1 8-1.1.1.1 8-1.1.1.2 11-1.1.1.1.1.1 15-1.1.1 16-1.1.1.2.1.1
(r / regulate-01~e.2
:ARG0~e.3 (p2 / phosphorylate-01~e.5
:ARG1~e.6 (a3 / and~e.15
:op1 (r2 / residue~e.8
:mod (a / amino-acid :mod 416~e.11
:name (n2 / name :op1 "tyrosine"~e.7)))
:op2 (r3 / residue~e.8
:mod (a4 / amino-acid :mod 527~e.16
:name (n3 / name :op1 "tyrosine"~e.7)))))
:ARG1 (p / protein
:name (n / name :op1 "Src"~e.0)))
# ::id pmid_1956_8237.126 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The expression of phosphorylated Src Y416 , which is associated with an active conformation , was low in the metastatic UM cell lines ( Figure 6A ) .
# ::alignments 1-1.1 2-1.1.1.r 3-1.1.1.3.2 4-1.1.1.3.1.1 9-1.1.2 10-1.1.2.1.r 12-1.1.2.1.1 13-1.1.2.1 16-1 17-1.2.r 19-1.2.1.3 21-1.2 22-1.2 25-1.3.1 26-1.3.1.1
(l / low-04~e.16
:ARG1 (e / express-03~e.1
:ARG2~e.2 (a3 / amino-acid :mod 416
:name (n3 / name :op1 "tyrosine")
:part-of (p2 / protein
:name (n / name :op1 "Src"~e.4)
:ARG3-of (p3 / phosphorylate-01~e.3)))
:ARG1-of (a / associate-01~e.9
:ARG2~e.10 (c / conformation~e.13
:ARG0-of (a2 / activity-06~e.12))))
:location~e.17 (c2 / cell-line~e.21,22
:mod (m2 / medical-condition
:name (n2 / name :op1 "melanoma")
:mod (u / uveal)
:ARG1-of (m / metastasize-101~e.19)))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.25 :mod "6A"~e.26)))
# ::id pmid_1956_8237.127 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Surprisingly , the phosphorylation of Y527 , which is associated with an inactive conformation , was also low , and a subsequent analysis indicated that Src expression is low in metastatic UM cell lines .
# ::alignments 0-1.1.3 3-1.1.1 9-1.1.1.2 10-1.1.1.2.1.r 12-1.1.1.2.1.1 12-1.1.1.2.1.1.1 12-1.1.1.2.1.1.1.r 13-1.1.1.2.1 16-1.1.2 17-1.1 19-1 21-1.2.1.1 21-1.2.1.1.r 22-1.2.1 23-1.2 24-1.2.2.r 25-1.2.2.1.1.1.1 26-1.2.2.1 28-1.2.2 29-1.2.2.1.2.r 30-1.2.2.1.2.1.3 32-1.2.2.1.2 33-1.2.2.1.2
(a / and~e.19
:op1 (l / low-04~e.17
:ARG1 (p / phosphorylate-01~e.3
:ARG1 (a2 / amino-acid :mod 527
:name (n / name :op1 "tyrosine"))
:ARG1-of (a3 / associate-01~e.9
:ARG2~e.10 (c / conformation~e.13
:ARG0-of (a4 / activity-06~e.12 :polarity~e.12 -~e.12))))
:mod (a5 / also~e.16)
:manner (s2 / surprise-01~e.0))
:op2 (i / indicate-01~e.23
:ARG0 (a6 / analyze-01~e.22
:time~e.21 (s / subsequent~e.21))
:ARG1~e.24 (l2 / low-04~e.28
:ARG1 (e / express-03~e.26
:ARG2 (p3 / protein
:name (n2 / name :op1 "Src"~e.25))
:ARG3~e.29 (c2 / cell-line~e.32,33
:mod (m2 / medical-condition
:name (n3 / name :op1 "melanoma")
:mod (u / uveal)
:ARG1-of (m / metastasize-101~e.30)))))))
# ::id pmid_1956_8237.128 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Therefore , the difference between kinase activity in metastatic cell lines ( OMM1 , OMM2.3 and OMM2.5 ) and UM cell lines ( OCM1 , OCM3 , OCM8 , Mel202 , Mel270 , Mel285 , Mel290 and 92.1 ) seems to be the result of a difference in Src expression .
# ::alignments 0-1 3-1.1.1.2 5-1.1.1.2.3.1 6-1.1.1.2.3 7-1.1.1.2.1.r 8-1.1.1.2.1.1 9-1.1.1.2.1 9-1.1.1.2.2 10-1.1.1.2.1 12-1.1.1.2.1.2.1.1.1.1 14-1.1.1.2.1.2.1.2.1.1 16-1.1.1.2.1.2.1.3.1.1 18-1.1.1.2.1.2.1 20-1.1.1.2.1.2.1.1 20-1.1.1.2.1.2.1.2 20-1.1.1.2.1.2.1.3 20-1.1.1.2.2.2.1.1 20-1.1.1.2.2.2.1.2 20-1.1.1.2.2.2.1.3 20-1.1.1.2.2.2.1.4 20-1.1.1.2.2.2.1.5 20-1.1.1.2.2.2.1.6 20-1.1.1.2.2.2.1.7 20-1.1.1.2.2.2.1.8 21-1.1.1.2.1.2.1.1 23-1.1.1.2.2.2.1.1.1.1 25-1.1.1.2.2.2.1.2.1.1 27-1.1.1.2.2.2.1.3.1.1 29-1.1.1.2.2.2.1.4.1.1 31-1.1.1.2.2.2.1.5.1.1 33-1.1.1.2.2.2.1.6.1.1 35-1.1.1.2.2.2.1.7.1.1 36-1.1.1.2.2.2.1 39-1.1 41-1.1.1.2.r 43-1.1.1 43-1.1.1.1 43-1.1.1.1.r 44-1.1.1.1.1.r 46-1.1.1.1.1 47-1.1.1.1.1.1.r 48-1.1.1.1.1.1.1.1.1 49-1.1.1.1.1.1
(c14 / cause-01~e.0
:ARG1 (s / seem-01~e.39
:ARG1 (t / thing~e.43
:ARG2-of~e.43 (r / result-01~e.43
:ARG1~e.44 (d / differ-02~e.46
:ARG3~e.47 (e / express-03~e.49
:ARG2 (p / protein
:name (n / name :op1 "Src"~e.48)))))
:domain~e.41 (d2 / differ-02~e.3
:ARG1~e.7 (c / cell-line~e.9,10
:ARG1-of (m / metastasize-101~e.8)
:ARG2-of (i / include-91
:ARG1 (a2 / and~e.18
:op1 (c2 / cell-line~e.20,21
:name (n2 / name :op1 "OMM1"~e.12))
:op2 (c3 / cell-line~e.20
:name (n3 / name :op1 "OMM2.3"~e.14))
:op3 (c4 / cell-line~e.20
:name (n4 / name :op1 "OMM2.5"~e.16)))))
:ARG2 (c5 / cell-line~e.9
:mod (m3 / medical-condition
:name (n5 / name :op1 "melanoma")
:mod (u / uveal))
:ARG1-of (m2 / mean-01
:ARG2 (a3 / and~e.36
:op1 (c6 / cell-line~e.20
:name (n6 / name :op1 "OCM1"~e.23))
:op2 (c7 / cell-line~e.20
:name (n7 / name :op1 "OCM3"~e.25))
:op3 (c8 / cell-line~e.20
:name (n8 / name :op1 "OCM8"~e.27))
:op4 (c9 / cell-line~e.20
:name (n9 / name :op1 "Mel202"~e.29))
:op5 (c10 / cell-line~e.20
:name (n10 / name :op1 "Mel270"~e.31))
:op6 (c11 / cell-line~e.20
:name (n11 / name :op1 "Mel285"~e.33))
:op7 (c12 / cell-line~e.20
:name (n12 / name :op1 "Mel290"~e.35))
:op8 (c13 / cell-line~e.20
:name (n13 / name :op1 "Mel292.1")))))
:ARG3 (a / activity-06~e.6
:ARG0 (k / kinase~e.5))))))
# ::id pmid_1956_8237.129 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To investigate the origin of a lowered Src expression , we performed a gene expression analysis ( Figure 6B ) .
# ::alignments 1-1.3 3-1.3.2 4-1.3.2.1.r 6-1.3.2.1.2 7-1.3.2.1.1.1.1 8-1.3.2.1 10-1.1 11-1 13-1.2.2.1 14-1.2.2 15-1.2 18-1.4.1 19-1.4.1.1
(p / perform-02~e.11
:ARG0 (w / we~e.10)
:ARG1 (a / analyze-01~e.15
:ARG0 w
:ARG1 (e / express-03~e.14
:ARG2 (g / gene~e.13)))
:purpose (i / investigate-01~e.1
:ARG0 w
:ARG1 (o / originate-01~e.3
:ARG1~e.4 (e2 / express-03~e.8
:ARG2 (p2 / protein
:name (n / name :op1 "Src"~e.7))
:ARG1-of (l / lower-05~e.6))))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.18 :mod "6B"~e.19)))
# ::id pmid_1956_8237.130 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Src gene expression varied widely in the cell lines and in the metastatic cell lines , but a correlation between protein and gene expression was not observed in UM cell lines .
# ::alignments 0-1.1.1.1.2.1 1-1.1.1.1 2-1.1.1 3-1.1 4-1.1.2 5-1.1.1.2.r 7-1.1.1.2.2 8-1.1.1.2.1 8-1.1.1.2.2 12-1.1.1.2.2.1 13-1.1.1.2.2 14-1.1.1.2.2 16-1 18-1.2.2 20-1.2.2.1.1 22-1.2.2.2.1 23-1.2.2.1 23-1.2.2.2 25-1.2.1 25-1.2.1.r 26-1.2 29-1.2.2.1.2 30-1.2.2.1.2
(c / contrast-01~e.16
:ARG1 (v / vary-01~e.3
:ARG0 (e / express-03~e.2
:ARG2 (g / gene~e.1 :wiki -
:name (n / name :op1 "Src"~e.0))
:ARG3~e.5 (a / and
:op1 (c2 / cell-line~e.8)
:op2 (c3 / cell-line~e.7,8,13,14
:ARG1-of (m / metastasize-101~e.12))))
:ARG1-of (w / wide-02~e.4))
:ARG2 (o / observe-01~e.26 :polarity~e.25 -~e.25
:ARG1 (c4 / correlate-01~e.18
:ARG1 (e2 / express-03~e.23
:ARG2 (p / protein~e.20)
:ARG3 (c5 / cell-line~e.29,30
:mod (m2 / medical-condition :wiki "Melanoma"
:name (n2 / name :op1 "melanoma")
:mod (u / uveal))))
:ARG2 (e3 / express-03~e.23
:ARG2 (g2 / gene~e.22)
:ARG3 c5))))
# ::id pmid_1956_8237.131 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok A western analysis of Src expression in UM and metastasis tissue revealed a very high Src expression in only one out of three primary UM , whereas all three metastasis tissues displayed medium expression of Src protein ( Figure 6C ) .
# ::alignments 1-1.1.1.2 2-1.1.1 3-1.1.1.1.r 4-1.1.1.1.1.1.1 5-1.1.1.1 8-1.1.1.1.2 9-1.1.1.1.2.2.1 10-1.1.1.1.2.2 11-1.1 13-1.1.2.3.1 14-1.1.2.3 15-1.1.2.1 16-1.1.2 17-1.1.2.4.r 18-1.1.2.4 19-1.1.2.2.1 22-1.1.2.2.3.1.1 23-1.1.2.2.3.1.3 26-1 27-1.2.1.3 28-1.2.1.1 29-1.2.1.2 30-1.2.1 31-1.2 32-1.2.2.2 33-1.2.2 34-1.2.2.1.r 35-1.2.2.1 36-1.2.2.1 39-1.3.1 40-1.3.1.1
(c / contrast-01~e.26
:ARG1 (r / reveal-01~e.11
:ARG0 (a / analyze-01~e.2
:ARG1~e.3 (e / express-03~e.5
:ARG2 (p / protein
:name (n2 / name :op1 "Src"~e.4))
:ARG3 (a2 / and~e.8
:op1 (m6 / medical-condition
:name (n3 / name :op1 "melanoma")
:mod (u / uveal))
:op2 (t / tissue~e.10
:mod (m / metastasis~e.9))))
:mod (w / western~e.1))
:ARG1 (e2 / express-03~e.16
:ARG2 p~e.15
:ARG3 (m4 / medical-condition :quant 1~e.19
:name (n4 / name :op1 "melanoma")
:ARG1-of (i / include-91
:ARG2 (m5 / medical-condition :quant 3~e.22
:name (n5 / name :op1 "melanoma")
:mod (p2 / primary~e.23)
:mod u))
:mod u)
:ARG1-of (h / high-02~e.14
:degree (v / very~e.13))
:mod~e.17 (o / only~e.18)))
:ARG2 (d4 / display-01~e.31
:ARG0 (t2 / tissue~e.30 :quant 3~e.28
:ARG1-of (m2 / metastasize-101~e.29)
:mod (a3 / all~e.27))
:ARG1 (e3 / express-03~e.33
:ARG2~e.34 p~e.35,36
:degree (m3 / medium~e.32)))
:ARG1-of (d5 / describe-01
:ARG0 (f / figure~e.39 :mod "6C"~e.40)))
# ::id pmid_1991_9690.1 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Expression and function of hypoxia inducible factor @-@ 1 alpha in human melanoma under non @-@ hypoxic conditions ( PMID : 19919690 )
# ::alignments 0-1.1 1-1 2-1.2 4-1.1.1.1.1 4-1.5.1 5-1.1.1.1.2 6-1.1.1.1.3 8-1.1.1.1.3 9-1.1.1.1.4 11-1.3.2 12-1.3.1.1 14-1.5.1.1 14-1.5.1.1.r 17-1.5
(a / and~e.1
:op1 (e / express-03~e.0
:ARG2 (p / protein
:name (n / name :op1 "hypoxia"~e.4 :op2 "inducible"~e.5 :op3 "factor-1"~e.6,8 :op4 "alpha"~e.9)))
:op2 (f / function-01~e.2
:ARG0 p)
:location (m / medical-condition
:name (n2 / name :op1 "melanoma"~e.12)
:mod (h / human~e.11))
:ARG1-of (d2 / describe-01
:ARG0 (p2 / publication-91 :ARG8 "PMID19919690"))
:ARG1-of (c / condition-01~e.17
:ARG2 (h2 / hypoxia~e.4 :polarity~e.14 -~e.14)))
# ::id pmid_1991_9690.6 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Results
# ::alignments 1-1 1-1.1 1-1.1.r
(t / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1))
# ::id pmid_1991_9690.7 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok HIF @-@ 1α mRNA and protein was increased in RGP vs melanocytes , VGP vs RGP and MET vs VGP melanoma cell lines .
# ::alignments 0-1.1.2 1-1.1.2 2-1.1.2 3-1.1.1.1.1 5-1.1.2 7-1 11-1.2.1.2 20-1.2.1.1.1.1.1 21-1.2.1.1 21-1.2.2.1 21-1.2.3.1 22-1.2.1.1 22-1.2.2.1 22-1.2.3.1
(i / increase-01~e.7
:ARG1 (a / and
:op1 (n3 / nucleic-acid
:name (n / name :op1 "mRNA"~e.3)
:ARG0-of (e / encode-01
:ARG1 (p / protein
:name (n2 / name :op1 "HIF-1α"))))
:op2 p~e.0,1,2,5)
:location (a2 / and
:op1 (c / contrast-01
:ARG1 (c2 / cell-line~e.21,22
:mod (m / medical-condition
:name (n6 / name :op1 "melanoma"~e.20))
:mod (p2 / phase
:mod (g / grow-01
:manner (r2 / radius))))
:ARG2 (m3 / melanocyte~e.11
:mod m))
:op2 (c4 / contrast-01
:ARG1 (c5 / cell-line~e.21,22
:mod m
:mod (p3 / phase
:mod (g2 / grow-01
:manner (v / vertical))))
:ARG2 c2)
:op3 (c7 / contrast-01
:ARG1 (c6 / cell-line~e.21,22
:mod m
:ARG1-of (m2 / metastasize-101))
:ARG2 c5)))
# ::id pmid_1991_9690.8 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We also detected expression of a HIF @-@ 1α mRNA splice variant that lacks part of the oxygen @-@ dependent regulation domain in WM1366 and WM9 melanoma cells .
# ::alignments 0-1.1 1-1.3 2-1 3-1.2 4-1.2.1.r 6-1.2.1.2.2.1.1.1 8-1.2.1.2.2.1.1.1 9-1.2.1.2.1.1 10-1.2.1.1 11-1.2.1 13-1.2.1.3 14-1.2.1.3.1.1.r 17-1.2.1.3.1.1.2.1 19-1.2.1.3.1.1.2 20-1.2.1.3.1.1.1 21-1.2.1.3.1.1 22-1.2.1.3.2.r 23-1.2.1.3.2.1.1.1 24-1.2.1.3.2 25-1.2.1.3.2.2.1.1 26-1.2.1.3.2.1.2.1.1 27-1.2.1.3.2.1 27-1.2.1.3.2.2
(d / detect-01~e.2
:ARG0 (w / we~e.0)
:ARG1 (e / express-03~e.3
:ARG2~e.4 (v / variant~e.11
:ARG1-of (s / splice-01~e.10)
:mod (n6 / nucleic-acid
:name (n / name :op1 "mRNA"~e.9)
:ARG0-of (e2 / encode-01
:ARG1 (p / protein
:name (n2 / name :op1 "HIF-1α"~e.6,8))))
:ARG0-of (l / lack-01~e.13
:ARG1 (t / thing
:part-of~e.14 (d2 / domain~e.21
:ARG0-of (r2 / regulate-01~e.20)
:ARG0-of (d3 / depend-01~e.19
:ARG1 (o / oxygen~e.17))))
:location~e.22 (a2 / and~e.24
:op1 (c / cell-line~e.27
:name (n3 / name :op1 "WM1366"~e.23)
:mod (m / medical-condition
:name (n4 / name :op1 "melanoma"~e.26)))
:op2 (c2 / cell-line~e.27
:name (n5 / name :op1 "WM9"~e.25)
:mod m)))))
:mod (a / also~e.1))
# ::id pmid_1991_9690.9 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Over @-@ expression of HIF @-@ 1α and its splice variant in the RGP cell line SbCl2 resulted in a small increase in soft agar colony formation and a large increase in matrigel invasion relative to control transfected cells .
# ::alignments 4-1.1.1.1.1.1 6-1.1.1.1.1.1 7-1.1.1 8-1.1.1.2.2 8-1.1.1.2.2.r 9-1.1.1.2.1 10-1.1.1.2 14-1.1.2 15-1.1.2 16-1.1.2.1.1 17-1 18-1.2.r 20-1.2.1.2 21-1.2.1 22-1.2.1.1.r 23-1.2.1.1.1.1.1 24-1.2.1.1.1.1 25-1.2.1.1.1 26-1.2.1.1 27-1.2 29-1.2.2.2 30-1.2.2 31-1.2.2.1.r 32-1.2.2.1.1.1.1 33-1.2.2.1 34-1.2.3 35-1.2.3.1.r 36-1.2.3.1.1 37-1.2.3.1.2 38-1.2.3.1
(r / result-01~e.17
:ARG1 (o / overexpress-01
:ARG1 (a2 / and~e.7
:op1 (p / protein
:name (n / name :op1 "HIF-1α"~e.4,6))
:op2 (v / variant~e.10
:ARG1-of (s / splice-01~e.9)
:poss~e.8 p~e.8))
:location (c / cell-line~e.14,15
:name (n2 / name :op1 "SbCl2"~e.16)
:mod (p3 / phase
:mod (g / grow-01
:manner (r3 / radius)))))
:ARG2~e.18 (a / and~e.27
:op1 (i / increase-01~e.21
:ARG1~e.22 (f / form-01~e.26
:ARG1 (c2 / colony~e.25
:mod (a3 / agar~e.24
:ARG1-of (s3 / soft-02~e.23))))
:mod (s2 / small~e.20))
:op2 (i2 / increase-01~e.30
:ARG1~e.31 (i3 / invade-01~e.33
:ARG0 (p2 / protein
:name (n4 / name :op1 "matrigel"~e.32)))
:mod (l / large~e.29))
:ARG1-of (r2 / relative-05~e.34
:ARG3~e.35 (c3 / cell~e.38
:mod (c4 / control~e.36)
:ARG1-of (t2 / transfect-01~e.37)))))
# ::id pmid_1991_9690.10 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Knockdown of HIF @-@ 1α expression by siRNA in the MET WM9 melanoma cell line resulted in a large decrease in both soft agar colony formation and matrigel invasion relative to cells treated with non @-@ specific siRNA .
# ::alignments 0-1.1 1-1.1.2.r 2-1.1.2.1.1.1 4-1.1.2.1.1.1 5-1.1.2 6-1.1.1.r 7-1.1.1.1.1 11-1.1.2.2.1.1 12-1.1.2.2.2.1.1 13-1.1.2.2 14-1.1.2.2 15-1 16-1.2.r 18-1.2.3 19-1.2 22-1.2.1.1.1.1.1 23-1.2.1.1.1.1 24-1.2.1.1.1 25-1.2.1.1 26-1.2.1 27-1.2.1.2.1.1.1 28-1.2.1.2 29-1.2.2 30-1.2.2.1.r 31-1.2.2.1 32-1.2.2.1.1 33-1.2.2.1.1.1.r 34-1.2.2.1.1.1.2.1 34-1.2.2.1.1.1.2.1.r 36-1.2.2.1.1.1 36-1.2.2.1.1.1.2 36-1.2.2.1.1.1.2.r 37-1.1.1.1.1 37-1.2.2.1.1.1.1.1
(r / result-01~e.15
:ARG1 (k / knock-down-02~e.0
:ARG0~e.6 (n5 / nucleic-acid
:name (n2 / name :op1 "siRNA"~e.7,37))
:ARG1~e.1 (e / express-03~e.5
:ARG2 (p / protein
:name (n / name :op1 "HIF-1α"~e.2,4))
:ARG3 (c / cell-line~e.13,14
:name (n3 / name :op1 "WM9"~e.11)
:mod (m / medical-condition
:name (n4 / name :op1 "melanoma"~e.12))
:ARG1-of (m2 / metastasize-101))))
:ARG2~e.16 (d2 / decrease-01~e.19
:ARG1 (a / and~e.26
:op1 (f / form-01~e.25
:ARG1 (c2 / colony~e.24
:mod (a2 / agar~e.23
:ARG1-of (s / soft-02~e.22))))
:op2 (i / invade-01~e.28
:ARG0 (p2 / protein
:name (n6 / name :op1 "matrigel"~e.27))))
:ARG1-of (r3 / relative-05~e.29
:ARG3~e.30 (c3 / cell~e.31
:ARG1-of (t2 / treat-04~e.32
:ARG2~e.33 (n8 / nucleic-acid~e.36
:name (n7 / name :op1 "siRNA"~e.37)
:ARG1-of~e.36 (s2 / specific-02~e.36 :polarity~e.34 -~e.34)))))
:mod (l / large~e.18)))
# ::id pmid_1991_9690.11 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok There is a high level of ERK1 @/@ 2 phosphorylation in WM9 cells , indicating an activated Ras @-@ Raf @-@ MEK @-@ ERK1 @/@ 2 MAPK pathway .
# ::alignments 3-1.1 4-1 5-1.2.r 6-1.2.1.1.1 8-1.2.1.1.1 9-1.2 10-1.2.2.r 11-1.2.2.1.1 12-1.2.2 14-1.3 16-1.3.1.2 17-1.3.1.1.1 19-1.3.1.1.1 21-1.3.1.1.1 23-1.3.1.1.1 25-1.3.1.1.1 26-1.3.1.1.2 27-1.3.1
(l2 / level~e.4
:ARG1-of (h / high-02~e.3)
:quant-of~e.5 (p / phosphorylate-01~e.9
:ARG1 (e / enzyme
:name (n2 / name :op1 "ERK1/2"~e.6,8))
:location~e.10 (c / cell-line~e.12
:name (n3 / name :op1 "WM9"~e.11)))
:ARG0-of (i / indicate-01~e.14
:ARG1 (p3 / pathway~e.27
:name (n4 / name :op1 "Ras-Raf-MEK-ERK1/2"~e.17,19,21,23,25 :op2 "MAPK"~e.26)
:ARG1-of (a / activate-01~e.16))))
# ::id pmid_1991_9690.12 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Treatment of WM9 cells with 30 μM U0126 MEK inhibitor , decreased ERK1 @/@ 2 phosphorylation and resulted in a decrease in HIF @-@ 1α expression .
# ::alignments 0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.1.1 3-1.1.1.1 4-1.1.1.2.r 5-1.1.1.2.3.1 6-1.1.1.2.3.2 7-1.1.1.2.1.1 8-1.1.1.2.2.1.1.1 9-1.1.1.2 9-1.1.1.2.2 9-1.1.1.2.2.r 11-1.1 12-1.1.2.1.1.1 14-1.1.2.1.1.1 15-1.1.2 16-1 17-1.2 18-1.2.2.r 20-1.2.2 21-1.2.2.1.r 22-1.2.2.1.1.1.1 24-1.2.2.1.1.1.1 25-1.2.2.1
(a / and~e.16
:op1 (d / decrease-01~e.11
:ARG0 (t2 / treat-04~e.0
:ARG1~e.1 (c / cell-line~e.3
:name (n3 / name :op1 "WM9"~e.2))
:ARG2~e.4 (s2 / small-molecule~e.9
:name (n4 / name :op1 "U0126"~e.7)
:ARG0-of~e.9 (i2 / inhibit-01~e.9
:ARG1 (p / protein-family
:name (n5 / name :op1 "MEK"~e.8)))
:quant (c2 / concentration-quantity :quant 30~e.5
:unit (m / micromolar~e.6))))
:ARG1 (p2 / phosphorylate-01~e.15
:ARG1 (e2 / enzyme
:name (n6 / name :op1 "ERK1/2"~e.12,14))))
:op2 (r / result-01~e.17
:ARG1 t2
:ARG2~e.18 (d2 / decrease-01~e.20
:ARG1~e.21 (e3 / express-03~e.25
:ARG2 (p3 / protein
:name (n7 / name :op1 "HIF-1α"~e.22,24))))))
# ::id pmid_1991_9690.13 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok However , a 24 h treatment with 10 μM U0126 totally eliminated Erk1 @/@ 2 phosphorylation , but did not change HIF @-@ 1 alpha levels .
# ::alignments 0-1 0-1.1 0-1.1.r 3-1.1.1.1.2.1 4-1.1.1.1.2.2 5-1.1.1.1 6-1.1.1.1.1.r 7-1.1.1.1.1.2.1 8-1.1.1.1.1.2.2 9-1.1.1.1.1.1.1 10-1.1.1.3 11-1.1.1 14-1.1.1.2.1.1.1 15-1.1.1.2 17-1.1 19-1.1.2.1 19-1.1.2.1.r 20-1.1.2 21-1.1.2.3.1.1.1 25-1.1.2.3
(c / contrast-01~e.0
:ARG2~e.0 (c2 / contrast-01~e.0,17
:ARG1 (e / eliminate-01~e.11
:ARG0 (t / treat-04~e.5
:ARG2~e.6 (s / small-molecule
:name (n / name :op1 "U0126"~e.9)
:quant (c3 / concentration-quantity :quant 10~e.7
:unit (m / micromolar~e.8)))
:duration (t2 / temporal-quantity :quant 24~e.3
:unit (h / hour~e.4)))
:ARG1 (p / phosphorylate-01~e.15
:ARG1 (e2 / enzyme
:name (n2 / name :op1 "ERK1/2"~e.14)))
:degree (t3 / total~e.10))
:ARG2 (c4 / change-01~e.20 :polarity~e.19 -~e.19
:ARG0 t
:ARG1 (l / level~e.25
:quant-of (p2 / protein
:name (n3 / name :op1 "HIF-1alpha"~e.21))))))
# ::id pmid_1991_9690.14 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Furthermore , siRNA knockdown of MEK siRNA did not change HIF @-@ 1 alpha levels .
# ::alignments 0-1 2-1.1.2.1.1.1 2-1.1.2.2.1.1 3-1.1.2 4-1.1.2.2.r 5-1.1.2.2.2.1.1.1 6-1.1.2.1.1.1 6-1.1.2.2.1.1 8-1.1.1 8-1.1.1.r 9-1.1 10-1.1.3.1.1.1 14-1.1.3
(a / and~e.0
:op2 (c / change-01~e.9 :polarity~e.8 -~e.8
:ARG0 (k / knock-down-02~e.3
:ARG0 (n / nucleic-acid
:name (n2 / name :op1 "siRNA"~e.2,6))
:ARG1~e.4 (n6 / nucleic-acid
:name (n3 / name :op1 "siRNA"~e.2,6)
:ARG0-of (e / encode-01
:ARG1 (e2 / enzyme
:name (n4 / name :op1 "MEK"~e.5)))))
:ARG1 (l / level~e.14
:quant-of (p2 / protein
:name (n5 / name :op1 "HIF-1alpha"~e.10)))))
# ::id pmid_1991_9690.47 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Results
# ::alignments 1-1 1-1.1 1-1.1.r
(t / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1))
# ::id pmid_1991_9690.48 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Expression of HIF @-@ 1α in human melanoma cells
# ::alignments 1-1 2-1.1.r 3-1.1.1.1 5-1.1.1.1 6-1.2.r 7-1.2.2 8-1.2.1.1.1 9-1.2
(e / express-03~e.1
:ARG2~e.2 (p / protein
:name (n / name :op1 "HIF-1α"~e.3,5))
:ARG3~e.6 (c / cell~e.9
:mod (m / medical-condition
:name (n2 / name :op1 "melanoma"~e.8))
:mod (h / human~e.7)))
# ::id pmid_1991_9690.49 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In addition to the well known pathway of HIF @-@ 1 alpha protein stabilization under hpoxic conditions , it has been established that many oncoproteins and growth factor signaling pathways up @-@ regulate HIF @-@ 1α expression under normoxic conditions [ @ 18 , 19 @ ] .
# ::alignments 0-1.1 1-1.2 2-1.2.1.r 4-1.2.1.2 5-1.2.1 6-1.2.1.1 7-1.2.1.1.1.r 8-1.2.1.1.1.1 9-1.2.1.1.1.1 10-1.2.1.1.1.1 11-1.2.1.1.1.1 12-1.2.1.1.1.1 13-1.2.1.1.1 16-1.1.2.2.2 16-1.2.1.1.1.2 21-1 22-1.1.r 23-1.1.1.1 24-1.1.1 25-1.1 26-1.1.2.3 27-1.1.2.3 28-1.1.2.1 29-1.1.2 33-1.1.2.2.1.1.1.1 35-1.1.2.2.1.1.1.1 36-1.1.2.2.1 39-1.1.2.2.2 39-1.2.1.1.1.2 42-1.3.1.1.1.1 46-1.3.1.1.1.2
(e / establish-01~e.21
:ARG1~e.22 (a / and~e.0,25
:op1 (o / oncoprotein~e.24
:quant (m / many~e.23))
:op2 (p / pathway~e.29
:ARG0-of (s2 / signal-07~e.28)
:ARG0-of (u / upregulate-01
:ARG1 (e2 / express-03~e.36
:ARG2 (p2 / protein
:name (n2 / name :op1 "HIF-1α"~e.33,35)))
:ARG1-of (c / condition-01~e.16,39
:ARG2 (n3 / normoxia)))
:mod (g / growth-factor~e.26,27)))
:ARG1-of (a2 / add-02~e.1
:ARG2~e.2 (k / know-01~e.5
:ARG1 (p3 / pathway~e.6
:ARG0-of~e.7 (s3 / stabilize-01~e.13
:ARG1 p2~e.8,9,10,11,12
:ARG1-of (c2 / condition-01~e.16,39
:ARG2 (h / hypoxia))))
:ARG1-of (w / well-09~e.4)))
:ARG1-of (d / describe-01
:ARG0 (p4 / publication
:ARG1-of (c3 / cite-01
:ARG2 (a3 / and :op1 18~e.42 :op2 19~e.46)))))
# ::id pmid_1991_9690.50 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok However , there are few investigations into the normoxic expression of HIF @-@ 1α in human melanoma and its role in the malignant progression of this disease .
# ::alignments 0-1 4-1.1.2 5-1.1 6-1.1.1.r 9-1.1.1.1 10-1.1.1.1.1.r 11-1.1.1.1.1.1.1 13-1.1.1.1.1.1.1 14-1.1.1.1.2.r 15-1.1.1.1.2.2 16-1.1.1.1.2.1.1 17-1.1.1 18-1.1.1.2.1 18-1.1.1.2.1.r 19-1.1.1.2 20-1.1.1.2.2.r 22-1.1.1.2.2.2 23-1.1.1.2.2
(c / contrast-01~e.0
:ARG2 (i / investigate-01~e.5
:ARG1~e.6 (a / and~e.17
:op1 (e / express-03~e.9
:ARG2~e.10 (p / protein
:name (n / name :op1 "HIF-1α"~e.11,13))
:ARG3~e.14 (m2 / medical-condition
:name (n2 / name :op1 "melanoma"~e.16)
:mod (h / human~e.15))
:mod (n3 / normoxia))
:op2 (r / role~e.19
:poss~e.18 e~e.18
:topic~e.20 (p2 / progress-01~e.23
:ARG1 m2
:ARG1-of (m / malignant-02~e.22))))
:quant (f / few~e.4)))
# ::id pmid_1991_9690.51 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Here , we show that in human melanoma cells , the oxygen @-@ labile HIF @-@ 1α protein as well as its mRNA is expressed endogenously under normoxic conditions .
# ::alignments 0-1.3 2-1.1 3-1 5-1.2.r 6-1.2.2.2 7-1.2.2.1.1.1 8-1.2.2 11-1.2.1.1.2.1 13-1.2.1.1.2 14-1.2.1.1.1.1 16-1.2.1.1.1.1 17-1.2.1.1 18-1.2.1 19-1.2.1 20-1.2.1 22-1.2.1.2.1.1 24-1.2 25-1.2.3 25-1.2.3.r 27-1.2.4.1 28-1.2.4
(s / show-01~e.3
:ARG0 (w / we~e.2)
:ARG1~e.5 (e / express-03~e.24
:ARG2 (a / and~e.18,19,20
:op1 (p / protein~e.17
:name (n2 / name :op1 "HIF-1α"~e.14,16)
:mod (l2 / labile~e.13
:topic (o / oxygen~e.11)))
:op2 (n5 / nucleic-acid
:name (n3 / name :op1 "mRNA"~e.22)
:ARG0-of (e2 / encode-01
:ARG1 p)))
:ARG3 (c / cell~e.8
:mod (m / medical-condition
:name (n / name :op1 "melanoma"~e.7))
:mod (h / human~e.6))
:manner~e.25 (e3 / endogenous~e.25)
:ARG1-of (c2 / condition-01~e.28
:ARG2 (n4 / normoxic~e.27)))
:medium (h2 / here~e.0))
# ::id pmid_1991_9690.52 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Figure 1A shows that HIF @-@ 1α protein is highly expressed in WM9 cells relative to normal human melanocyte ( HEMn @-@ LP ) , but radial growth phase ( SbCl2 ) , and vertical growth phase ( WM1366 ) also express a higher amount of HIF @-@ 1α protein relative to human melanocytes .
# ::alignments 0-1.1 2-1.1.1 4-1 5-1.2.r 6-1.2.1.1.1.1 8-1.2.1.1.1.1 9-1.2.1.1 11-1.2.1.3 12-1.2.1 14-1.2.1.2.1.1 15-1.2.1.2 15-1.2.1.4.1.3.1 15-1.2.2.2.1.2 15-1.2.2.2.2.2 16-1.2.1.4 17-1.2.1.4.1.r 18-1.2.1.4.1.1 19-1.2.1.4.1.2 20-1.2.1.4.1 22-1.2.1.4.1.3.1.1.1 24-1.2.1.4.1.3.1.1.1 27-1.2 28-1.2.2.2.1.1.1 29-1.2.2.2.1.1 30-1.2.2.2.1 35-1.2.2.2 36-1.2.2.2.2.1.1 37-1.2.2.2.2.1 38-1.2.2.2.2 40-1.2.2.2.2.2.1.1 42-1.2.2.3 43-1.2.2 45-1.2.2.1.2 45-1.2.2.1.2.1 45-1.2.2.1.2.1.r 46-1.2.2.1 47-1.2.2.1.1.r 48-1.2.2.1.1 49-1.2.2.1.1 50-1.2.2.1.1 51-1.2.2.1.1 52-1.2.2.4 53-1.2.2.4.1.r 54-1.2.2.4.1.1 55-1.2.2.4.1
(s / show-01~e.4
:ARG0 (f / figure~e.0 :mod "1A"~e.2)
:ARG1~e.5 (c / contrast-01~e.27
:ARG1 (e / express-03~e.12
:ARG2 (p / protein~e.9
:name (n / name :op1 "HIF-1α"~e.6,8))
:ARG3 (c2 / cell-line~e.15
:name (n2 / name :op1 "WM9"~e.14))
:ARG1-of (h2 / high-02~e.11)
:ARG1-of (r / relative-05~e.16
:ARG3~e.17 (m3 / melanocyte~e.20
:ARG1-of (n9 / normal-02~e.18)
:mod (h3 / human~e.19)
:ARG1-of (m2 / mean-01
:ARG2 (c7 / cell-line~e.15
:name (n8 / name :op1 "HEMn-LP"~e.22,24))))))
:ARG2 (e2 / express-03~e.43
:ARG2 (a3 / amount-01~e.46
:ARG1~e.47 p~e.48,49,50,51
:ARG1-of (h / high-02~e.45
:degree~e.45 (m / more~e.45)))
:ARG3 (a / and~e.35
:op1 (p2 / phase~e.30
:mod (g / grow-01~e.29
:manner (r2 / radius~e.28))
:example (c4 / cell-line~e.15
:name (n5 / name :op1 "SbCI2")))
:op2 (p3 / phase~e.38
:mod (g2 / grow-01~e.37
:manner (v / vertical~e.36))
:example (c5 / cell-line~e.15
:name (n6 / name :op1 "WM1366"~e.40))))
:mod (a2 / also~e.42)
:ARG1-of (r3 / relative-05~e.52
:mod~e.53 (m4 / melanocyte~e.55
:mod h3~e.54)))))
# ::id pmid_1991_9690.53 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Similar results are seen in second set of RGP , VGP and MET melanoma cell lines ( Fig . 1B ) .
# ::alignments 0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 3-1 4-1.2.r 5-1.2.1 5-1.2.1.1 5-1.2.1.1.r 6-1.2 11-1.2.2 13-1.2.2.4.1.1 14-1.2.2.1 14-1.2.2.2 14-1.2.2.3 15-1.2.2.1 17-1.3.1 20-1.3.1.1
(s / see-01~e.3
:ARG1 (t / thing~e.1
:ARG2-of~e.1 (r2 / result-01~e.1)
:ARG1-of (r / resemble-01~e.0))
:location~e.4 (s2 / set~e.6
:ord (o / ordinal-entity~e.5 :value~e.5 2~e.5)
:consist-of (a / and~e.11
:op1 (c / cell-line~e.14,15
:mod (p / phase
:mod (g / grow-01
:manner (r3 / radius))))
:op2 (c2 / cell-line~e.14
:mod (p2 / phase
:mod (g2 / grow-01
:manner (v / vertical))))
:op3 (c3 / cell-line~e.14
:ARG1-of (m2 / metastasize-101))
:mod (m / medical-condition
:name (n / name :op1 "melanoma"~e.13))))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.17 :mod "1B"~e.20)))
# ::id pmid_1991_9690.54 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok HIF @-@ 1α was detected as 120 kD protein in nuclear extracts while no protein was detected in cytoplasmic extracts ( data not shown ) .
# ::alignments 0-1.1.1.1.1 2-1.1.1.1.1 4-1.2 6-1.1.1.2.1 8-1.2.2 10-1.1.2.2 11-1.1.2 11-1.1.2.1 11-1.1.2.1.r 11-1.2.3 11-1.2.3.1 11-1.2.3.1.r 12-1 13-1.2.1 13-1.2.1.r 14-1.2.2 16-1.1 16-1.2 18-1.2.3.2 19-1.1.2 19-1.1.2.1 19-1.1.2.1.r 19-1.2.3 19-1.2.3.1 19-1.2.3.1.r 21-1.3.1 22-1.3.1.1.1 22-1.3.1.1.1.r 23-1.3.1.1
(c / contrast-01~e.12
:ARG1 (d / detect-01~e.16
:ARG1 (p / protein
:name (n / name :op1 "HIF-1α"~e.0,2)
:quant (m / mass-quantity :quant 120~e.6
:unit (k / kilodalton)))
:location (t / thing~e.11,19
:ARG1-of~e.11,19 (e / extract-01~e.11,19)
:mod (n2 / nucleus~e.10)))
:ARG2 (d2 / detect-01~e.4,16 :polarity~e.13 -~e.13
:ARG1 (p2 / protein~e.8,14)
:location (t2 / thing~e.11,19
:ARG1-of~e.11,19 (e2 / extract-01~e.11,19)
:mod (c2 / cytoplasm~e.18)))
:ARG1-of (d3 / describe-01
:ARG0 (d4 / data~e.21
:ARG1-of (s / show-01~e.23 :polarity~e.22 -~e.22))))
# ::id pmid_1991_9690.55 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Hypoxic stabilization of HIF @-@ 1α occurs at the protein level [ @ 3 @ ] .
# ::alignments 1-1 2-1.1.r 3-1.1.1.1 5-1.1.1.1 7-1.2.r 9-1.2.1 10-1.2 13-1.4.1.1.1
(s / stabilize-01~e.1
:ARG1~e.2 (p / protein
:name (n / name :op1 "HIF-1α"~e.3,5))
:ARG2~e.7 (l / level~e.10
:quant-of (p2 / protein~e.9))
:mod (h / hypoxia)
:ARG1-of (d / describe-01
:ARG0 (p3 / publication
:ARG1-of (c / cite-01 :ARG2 3~e.13))))
# ::id pmid_1991_9690.56 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Since HIF @-@ 1α protein was increased in human melanoma cells under normoxic conditions , we determined whether this increase might be due to increased HIF @-@ 1α mRNA levels .
# ::alignments 0-1.3 1-1.3.1.1 2-1.3.1.1 3-1.3.1.1 4-1.3.1.1 6-1.3.1 7-1.3.1.2.r 8-1.3.1.2.2 9-1.3.1.2.1.1.1 10-1.3.1.2 13-1.3.1.2.3 15-1.1 16-1 17-1.2.1 17-1.2.1.r 18-1.2.2.2.1 19-1.2.2.2 20-1.2 22-1.2.2 23-1.2.2 24-1.2.2.1.2 24-1.2.2.2 25-1.2.2.1.1.2.1.1.1 27-1.2.2.1.1.2.1.1.1 28-1.2.2.1.1.1.1 29-1.2.2.1
(d / determine-01~e.16
:ARG0 (w / we~e.15)
:ARG1 (p2 / possible-01~e.20 :mode~e.17 interrogative~e.17
:ARG1 (c / cause-01~e.22,23
:ARG0 (l / level~e.29
:quant-of (n5 / nucleic-acid
:name (n / name :op1 "mRNA"~e.28)
:ARG0-of (e / encode-01
:ARG1 (p3 / protein
:name (n2 / name :op1 "HIF-1α"~e.25,27))))
:ARG1-of (i3 / increase-01~e.24))
:ARG1 (i / increase-01~e.19,24
:mod (t / this~e.18))))
:ARG1-of (c4 / cause-01~e.0
:ARG0 (i2 / increase-01~e.6
:ARG1 p3~e.1,2,3,4
:location~e.7 (c2 / cell~e.10
:mod (m / medical-condition
:name (n3 / name :op1 "melanoma"~e.9))
:mod (h / human~e.8)
:ARG1-of (c3 / condition-01~e.13
:ARG2 (n4 / normoxia))))))
# ::id pmid_1991_9690.57 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Initially we used semi @-@ quantitative RT @-@ PCR to assess expression of HIF @-@ 1α full length ( FL ) and a splice variant HIF @-@ 1α785 that is missing the acetylation site lys @ 532 @ due to lack of exon 11 ( Fig . 2A ) .
# ::alignments 0-1.4 1-1.1 2-1 3-1.2.2.1 5-1.2.2 6-1.2.1.1 8-1.2.1.1 10-1.3 11-1.3.2.1 12-1.3.2.1.1.r 13-1.3.2.1.1.1.1 15-1.3.2.1.1.1.1 16-1.3.2.1.2.1 17-1.3.2.1.2 21-1.3.2 23-1.3.2.2.1 24-1.3.2.2 25-1.3.2.2.2.1.1.1 27-1.3.2.2.2.1.1.1 30-1.3.2.2.3 32-1.3.2.2.3.1.1 33-1.3.2.2.3.1 34-1.3.2.2.3.1.2.2.1 36-1.3.2.2.3.1.2.1 38-1.3.2.2.3.2 39-1.3.2.2.3.2 40-1.3.2.2.3.2.1 41-1.3.2.2.3.2.1.1.r 42-1.3.2.2.3.2.1.1 43-1.3.2.2.3.2.1.1.1 45-1.5.1 48-1.5.1.1
(u / use-01~e.2
:ARG0 (w / we~e.1)
:ARG1 (t / thing
:name (n / name :op1 "RT-PCR"~e.6,8)
:mod (q / quantitative~e.5
:degree (s / semi~e.3)))
:ARG2 (a / assess-01~e.10
:ARG0 w
:ARG1 (a2 / and~e.21
:op1 (e / express-03~e.11
:ARG2~e.12 (p / protein
:name (n2 / name :op1 "HIF-1α"~e.13,15))
:ARG1-of (l / long-03~e.17
:degree (f / full~e.16)))
:op2 (v / variant~e.24
:ARG1-of (s2 / splice-01~e.23)
:ARG1-of (m2 / mean-01
:ARG2 (p2 / protein
:name (n4 / name :op1 "HIF-1α785"~e.25,27)))
:ARG0-of (m / miss-01~e.30
:ARG1 (s3 / site-01~e.33
:ARG0-of (a4 / acetylate-01~e.32)
:mod (a3 / amino-acid :mod 532~e.36
:name (n3 / name :op1 "lysine"~e.34)))
:ARG1-of (c / cause-01~e.38,39
:ARG0 (l2 / lack-01~e.40
:ARG1~e.41 (e2 / exon~e.42 :mod 11~e.43)))))))
:time (i / initial~e.0)
:ARG1-of (d / describe-01
:ARG0 (f2 / figure~e.45 :mod "2A"~e.48)))
# ::id pmid_1991_9690.58 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok This splice variant encodes HIF @-@ 1α protein that has been reported to be stable under normoxic conditions [ @ 17 , 20 @ ] .
# ::alignments 0-1.1.2 1-1.1.1 2-1.1 3-1 4-1.2.1.1 6-1.2.1.1 7-1.2 11-1.2.2.2 14-1.2.2 17-1.2.2.1 20-1.3.1.1.1.1 24-1.3.1.1.1.2
(e / encode-01~e.3
:ARG0 (v / variant~e.2
:ARG1-of (s / splice-01~e.1)
:mod (t / this~e.0))
:ARG1 (p / protein~e.7
:name (n / name :op1 "HIF-1α"~e.4,6)
:ARG1-of (s2 / stable-03~e.14
:ARG1-of (c / condition-01~e.17
:ARG2 (n2 / normoxia))
:ARG1-of (r / report-01~e.11)))
:ARG1-of (d / describe-01
:ARG0 (p2 / publication
:ARG1-of (c2 / cite-01
:ARG2 (a / and :op1 17~e.20 :op2 20~e.24)))))
# ::id pmid_1991_9690.59 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Primers were designed so that full length HIF @-@ 1α would exclude HIF @-@ 1α785 by targeting exon 11 , which is absent in HIF @-@ 1α785 .
# ::alignments 0-1.1 2-1 5-1.2.1.2.1 6-1.2.1 6-1.2.1.2 6-1.2.1.2.r 7-1.2.1.1.1 9-1.2.1.1.1 11-1.2 12-1.2.1.1.1 12-1.2.2.1.1 14-1.2.2.1.1 15-1.2.3.r 16-1.2.3 17-1.2.3.2 18-1.2.3.2.1 22-1.2.3.2.2 24-1.2.1.1.1 24-1.2.2.1.1 26-1.2.2.1.1
(d / design-01~e.2
:ARG1 (p3 / primer~e.0)
:ARG3 (e / exclude-01~e.11
:ARG0 (p / protein~e.6
:name (n2 / name :op1 "HIF-1α"~e.7,9,12,24)
:ARG1-of~e.6 (l2 / long-03~e.6
:degree (f / full~e.5)))
:ARG1 (p2 / protein
:name (n3 / name :op1 "HIF-1α785"~e.12,14,24,26))
:manner~e.15 (t / target-01~e.16
:ARG0 p
:ARG1 (e2 / exon~e.17 :mod 11~e.18
:ARG1-of (a / absent-01~e.22
:ARG2 p2)))))
# ::id pmid_1991_9690.60 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Primers for HIF @-@ 1α785 excluded HIF @-@ 1α by targeting the exon 10 @:@ 12 boundary only present in HIF @-@ 1α785 .
# ::alignments 0-1.1 2-1.1.1.1.1 2-1.2.1.1 5-1 6-1.1.1.1.1 6-1.2.1.1 8-1.2.1.1 9-1.3.r 10-1.3 12-1.3.2.2.1 12-1.3.2.2.2 13-1.3.2.2.1.1 15-1.3.2.2.2.1 16-1.3.2 17-1.3.2.1.2 18-1.3.2.1 20-1.1.1.1.1 20-1.2.1.1
(e / exclude-01~e.5
:ARG0 (p4 / primer~e.0
:beneficiary (p / protein
:name (n2 / name :op1 "HIF-1α758"~e.2,6,20)))
:ARG1 (p2 / protein
:name (n3 / name :op1 "HIF-1α"~e.2,6,8,20))
:manner~e.9 (t / target-01~e.10
:ARG0 p4
:ARG1 (b / boundary~e.16
:ARG1-of (p3 / present-02~e.18
:ARG2 p
:mod (o / only~e.17))
:mod (b2 / between
:op1 (e2 / exon~e.12 :mod 10~e.13)
:op2 (e3 / exon~e.12 :mod 12~e.15)))))
# ::id pmid_1991_9690.61 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Fig. 2B shows that human melanoma cell lines express both full @-@ length and the 785 splice variant HIF @-@ 1α mRNA at a level that appeared to be higher than normal human melanocytes .
# ::alignments 0-1.1 2-1.1.1 4-1 5-1.2.r 6-1.2.2.2 7-1.2.2.1.1.1 8-1.2.2 9-1.2.2 10-1.2 12-1.2.1.1.2.1.2.1 14-1.2.1.1.2.1 14-1.2.1.1.2.1.2 14-1.2.1.1.2.1.2.r 15-1.2.1 18-1.2.1.2.2.1.1 19-1.2.1.2.2.1 20-1.2.1.1.2.1.1.1 20-1.2.1.2.2.1.2.1.1.1 22-1.2.1.1.2.1.1.1 23-1.2.1.1.1.1 23-1.2.1.2.1.1 24-1.2.3.r 26-1.2.3 28-1.2.3.1 31-1.2.3.2 31-1.2.3.2.1 31-1.2.3.2.1.r 32-1.2.3.2.2.r 33-1.2.3.2.2.1 34-1.2.3.2.2.2 35-1.2.3.2.2
(s / show-01~e.4
:ARG0 (f / figure~e.0 :mod "2B"~e.2)
:ARG1~e.5 (e / express-03~e.10
:ARG2 (a / and~e.15
:op1 (n6 / nucleic-acid
:name (n2 / name :op1 "mRNA"~e.23)
:ARG0-of (e2 / encode-01
:ARG1 (p / protein~e.14
:name (n3 / name :op1 "HIF-1α"~e.20,22)
:ARG1-of~e.14 (l3 / long-03~e.14
:degree (f2 / full~e.12)))))
:op2 (n7 / nucleic-acid
:name (n4 / name :op1 "mRNA"~e.23)
:ARG0-of (e3 / encode-01
:ARG1 (v / variant~e.19
:ARG1-of (s2 / splice-01~e.18)
:ARG1-of (m2 / mean-01
:ARG2 (p2 / protein
:name (n5 / name :op1 "HIF-1α785"~e.20)))))))
:ARG3 (c / cell-line~e.8,9
:mod (m4 / medical-condition
:name (n / name :op1 "melanoma"~e.7))
:mod (h2 / human~e.6))
:manner~e.24 (l2 / level~e.26
:ARG1-of (a2 / appear-01~e.28)
:ARG1-of (h / high-02~e.31
:degree~e.31 (m / more~e.31)
:compared-to~e.32 (m3 / melanocyte~e.35
:ARG1-of (n8 / normal-02~e.33)
:mod (h3 / human~e.34))))))
# ::id pmid_1991_9690.62 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok These findings were verified by qRT @-@ PCR measurement of full @-@ length and HIF @-@ 1α785 mRNA levels ( Fig . 3 ) .
# ::alignments 0-1.2.2 1-1.2 1-1.2.1 1-1.2.1.r 3-1 7-1.1.2.1.1 8-1.1 9-1.1.1.r 10-1.1.1.1.1.2.1 12-1.1.1.1.1 12-1.1.1.1.1.2 12-1.1.1.1.1.2.r 13-1.1.1 14-1.1.1.2.1.2.1.1.1 16-1.1.1.2.1.2.1.1.1 17-1.1.1.1.1.1.1 17-1.1.1.2.1.1.1 18-1.1.1.1 18-1.1.1.2 20-1.3.1 23-1.3.1.1
(v / verify-01~e.3
:ARG0 (m / measure-01~e.8
:ARG1~e.9 (a / and~e.13
:op1 (l / level~e.18
:quant-of (n3 / nucleic-acid~e.12
:name (n2 / name :op1 "mRNA"~e.17)
:ARG1-of~e.12 (l4 / long-03~e.12
:degree (f2 / full~e.10))))
:op2 (l3 / level~e.18
:quant-of (n6 / nucleic-acid
:name (n4 / name :op1 "mRNA"~e.17)
:ARG0-of (e2 / encode-01
:ARG1 (p2 / protein-segment
:name (n5 / name :op1 "HIF-1α785"~e.14,16))))))
:mod (t3 / thing
:name (n / name :op1 "RT-PCR"~e.7)
:mod (q / quantitative)))
:ARG1 (t / thing~e.1
:ARG1-of~e.1 (f / find-01~e.1)
:mod (t2 / this~e.0))
:ARG1-of (d / describe-01
:ARG0 (f3 / figure~e.20 :mod 3~e.23)))
# ::id pmid_1991_9690.63 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok All melanoma cell lines had increased expression of HIF @-@ 1α mRNA relative to normal human melanocytes .
# ::alignments 0-1.1.2.2 1-1.1.2.1.1.1 2-1.1.2 3-1.1.2 5-1 6-1.1 7-1.1.1.r 8-1.1.1.2.1.1.1 10-1.1.1.2.1.1.1 11-1.1.1.1.1 12-1.1.3 13-1.1.3.1.r 14-1.1.3.1.1 15-1.1.3.1.2 16-1.1.3.1
(i / increase-01~e.5
:ARG1 (e / express-03~e.6
:ARG2~e.7 (n4 / nucleic-acid
:name (n2 / name :op1 "mRNA"~e.11)
:ARG0-of (e2 / encode-01
:ARG1 (p / protein
:name (n3 / name :op1 "HIF-1α"~e.8,10))))
:ARG3 (c / cell-line~e.2,3
:mod (m2 / medical-condition
:name (n / name :op1 "melanoma"~e.1))
:mod (a / all~e.0))
:ARG1-of (r2 / relative-05~e.12
:ARG3~e.13 (m / melanocyte~e.16
:ARG1-of (n6 / normal-02~e.14)
:mod (h / human~e.15)))))
# ::id pmid_1991_9690.64 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In addition VGP and MET cell lines expressed more of the 785 HIF @-@ 1α mRNA than full length HIF @-@ 1α mRNA .
# ::alignments 0-1.1.2 1-1.1.2 3-1.1.2 5-1.1.2.1 5-1.1.2.2 6-1.1.2.1 7-1.1 7-1.1.3 8-1.1.4 12-1.1.1.2.1.1.1 12-1.1.3.1.2.1.1.1 14-1.1.3.1.2.1.1.1 15-1.1.3.1.1.1 16-1.1.3.r 17-1.1.3.1.2.1.2.1 18-1.1.3.1.2.1 18-1.1.3.1.2.1.2 18-1.1.3.1.2.1.2.r 19-1.1.3.1.2.1.1.1 21-1.1.3.1.2.1.1.1 22-1.1.1.1.1 22-1.1.3.1.1.1
(a / and
:op2 (e / express-03~e.7
:ARG2 (n / nucleic-acid
:name (n3 / name :op1 "mRNA"~e.22)
:ARG0-of (e2 / encode-01
:ARG1 (p / protein
:name (n4 / name :op1 "HIF-1α785"~e.12))))
:ARG3 (a2 / and~e.0,1,3
:op1 (c / cell-line~e.5,6
:mod (p3 / phase
:mod (g / grow-01
:manner (v / vertical))))
:op2 (c2 / cell-line~e.5
:mod (m2 / metastasis)))
:compared-to~e.16 (e3 / express-03~e.7
:ARG2 (n2 / nucleic-acid
:name (n5 / name :op1 "mRNA"~e.15,22)
:ARG0-of (e4 / encode-01
:ARG1 (p2 / protein~e.18
:name (n6 / name :op1 "HIF-1α"~e.12,14,19,21)
:ARG1-of~e.18 (l2 / long-03~e.18
:degree (f / full~e.17)))))
:ARG3 a2)
:degree (m / more~e.8)))
# ::id pmid_1991_9690.65 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Overall the WM9 metastatic melanoma expressed the highest amount of 785 HIF @-@ 1α mRNA (~ 79× higher than normal human melanocytes ) .
# ::alignments 0-1.3 2-1.2.1.1 3-1.2.2.2 4-1.2.2.1.1 5-1 7-1.1.2 7-1.1.2.1 7-1.1.2.1.r 7-1.1.3 7-1.1.3.1 7-1.1.3.1.r 8-1.1 9-1.1.2.2.1 11-1.1.1.2.1.1.1 14-1.1.1.1.1 17-1.1.2 17-1.1.2.1 17-1.1.2.1.r 18-1.1.2.3.r 19-1.1.2.3.1 20-1.1.2.3.2 21-1.1.2.3
(e / express-03~e.5
:ARG2 (a / amount-01~e.8
:ARG1 (n5 / nucleic-acid
:name (n3 / name :op1 "mRNA"~e.14)
:ARG0-of (e2 / encode-01
:ARG1 (p / protein-segment
:name (n4 / name :op1 "HIF-1α785"~e.11))))
:ARG2 (h2 / high-02~e.7,17
:degree~e.7,17 (m2 / more~e.7,17)
:mod (a2 / approximately
:op1 (p2 / product-of~e.9 :op1 79))
:compared-to~e.18 (m3 / melanocyte~e.21
:ARG1-of (n7 / normal-02~e.19)
:mod (h3 / human~e.20)))
:ARG1-of (h / high-02~e.7
:degree~e.7 (m / most~e.7)))
:ARG3 (c / cell-line
:name (n / name :op1 "WM9"~e.2)
:mod (m5 / medical-condition
:name (n2 / name :op1 "melanoma"~e.4)
:ARG1-of (m4 / metastasize-101~e.3)))
:mod (o / overall~e.0))
# ::id pmid_1991_9690.66 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok HIFαFL and HIF @-@ 1α785 gain @-@ of @-@ function in radial growth phase SbCl2 cells
# ::alignments 2-1.1 3-1.1.2.1.1 5-1.1.2.1.1 6-1.3 10-1.3.2 12-1.2.2.1.1 13-1.2.2.1 14-1.2.2 15-1.2.1.1 16-1.2
(m / mutate-01
:ARG1 (a / and~e.2
:op1 (p / protein
:name (n / name :op1 "HIFα")
:ARG1-of (l2 / long-03
:degree (f / full)))
:op2 (p2 / protein-segment
:name (n2 / name :op1 "HIF-1α785"~e.3,5)))
:location (c / cell-line~e.16
:name (n3 / name :op1 "SbCl2"~e.15)
:mod (p3 / phase~e.14
:mod (g2 / grow-01~e.13
:manner (r / radius~e.12))))
:manner (g3 / gain-02~e.6
:ARG0 a
:ARG1 (f2 / function-01~e.10)))
# ::id pmid_1991_9690.67 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The level of HIF @-@ 1α protein is low in the radial growth phase SbCl2 cells relative to VGP or MET cell lines .
# ::alignments 1-1.1 2-1.1.1.r 3-1.1.1.1.1 5-1.1.1.1.1 6-1.1.1 8-1 9-1.2.r 11-1.2.2.1.1 12-1.2.2.1 12-1.3.1.1.1.1 13-1.2.2 13-1.3.1.1.1 14-1.2.1.1 15-1.3.1.1 15-1.3.1.2 16-1.3 21-1.3.1.2 22-1.3.1.2
(l / low-04~e.8
:ARG1 (l2 / level~e.1
:quant-of~e.2 (p / protein~e.6
:name (n / name :op1 "HIF-1α"~e.3,5)))
:location~e.9 (c / cell-line
:name (n2 / name :op1 "SbCl2"~e.14)
:mod (p2 / phase~e.13
:mod (g / grow-01~e.12
:manner (r / radius~e.11))))
:ARG1-of (r2 / relative-05~e.16
:ARG3 (a / and
:op1 (c2 / cell-line~e.15
:mod (p3 / phase~e.13
:mod (g2 / grow-01~e.12
:manner (v / vertical))))
:op2 (c3 / cell-line~e.15,21,22
:ARG1-of (m / metastasize-101)))))
# ::id pmid_1991_9690.68 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We determined the effect of HIF @-@ 1αFL or HIF @-@ 1α785 overexpression on SbCl2 anchorage @-@ independent growth and Matrigel invasion .
# ::alignments 0-1.1 1-1 3-1.2 4-1.2.1.r 5-1.2.1.1.1.2.1 5-1.2.1.1.2.2.1 8-1.2.1.1 9-1.2.1.1.1.2.1 9-1.2.1.1.2.2.1 11-1.2.1.1.2.2.1 12-1.2.1 13-1.2.1.2.r 14-1.2.1.2.2.1 15-1.2.2.1.1.2 17-1.2.2.1.1 17-1.2.2.1.1.1 17-1.2.2.1.1.1.r 18-1.2.2.1 19-1.2.2 20-1.2.2.2.1.2.1 21-1.2.2.2
(d / determine-01~e.1
:ARG0 (w / we~e.0)
:ARG1 (a / affect-01~e.3
:ARG0~e.4 (o / overexpress-01~e.12
:ARG1 (o2 / or~e.8
:op1 (p / protein :wiki "HIF1A"
:name (n / name :op1 "HIF-1α"~e.5,9)
:ARG1-of (l2 / long-03
:degree (f / full)))
:op2 (p2 / protein :wiki -
:name (n2 / name :op1 "HIF-1α785"~e.5,9,11)))
:location~e.13 (c / cell-line :wiki -
:name (n4 / name :op1 "SbCl2"~e.14)))
:ARG1 (a2 / and~e.19
:op1 (g / grow-01~e.18
:ARG0-of (d2 / depend-01~e.17 :polarity~e.17 -~e.17
:ARG1 (a3 / anchorage~e.15)))
:op2 (i / invade-01~e.21
:ARG0 (p3 / protein :wiki "Matrigel"
:name (n3 / name :op1 "Matrigel"~e.20))))))
# ::id pmid_1991_9690.69 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok HIF @-@ 1αFL and HIF @-@ 1α785 were cloned into the pLenti @-@ V5 @-@ D @-@ TOPO vector and transiently overexpressed in SbCl2 cells ( Fig . 4A ) .
# ::alignments 0-1.1.1.1.1.1 0-1.1.1.2.1.1 4-1.1.1.1.1.1 4-1.1.1.2.1.1 6-1.1.1.2.1.1 8-1.1 9-1.1.2.r 11-1.1.2.1.1 13-1.1.2.1.1 15-1.1.2.1.1 17-1.1.2.1.1 18-1.1.2 19-1 20-1.2.2 21-1.2 22-1.2.3.r 23-1.2.3.1.1 24-1.2.3 26-1.3.1 29-1.3.1.1
(a / and~e.19
:op1 (c / clone-01~e.8
:ARG1 (a2 / and
:op1 (p / protein
:name (n / name :op1 "HIF-1α"~e.0,4)
:ARG1-of (l2 / long-03
:degree (f3 / full)))
:op2 (p2 / protein
:name (n2 / name :op1 "HIF-1α785"~e.0,4,6)))
:instrument~e.9 (v / vector~e.18
:name (n3 / name :op1 "pLenti-V5-D-TOPO"~e.11,13,15,17)))
:op2 (o / overexpress-01~e.21
:ARG1 a2
:ARG1-of (t / transient-02~e.20)
:location~e.22 (c2 / cell-line~e.24
:name (n4 / name :op1 "SbCl2"~e.23)))
:ARG1-of (d / describe-01
:ARG0 (f2 / figure~e.26 :mod "4A"~e.29)))
# ::id pmid_1991_9690.70 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok HIF @-@ 1α785 overexpression resulted in a small , but statistically significant increase in anchorage @-@ independent growth , relative to mock or lacz transfected cells ( Fig . 4C and 4D ) .
# ::alignments 0-1.1.1.1.1 2-1.1.1.1.1 3-1.1 4-1 5-1.2.r 7-1.2.2 9-1.2.2.1 10-1.2.2.1.1.1 11-1.2.2.1.1 12-1.2 13-1.2.1.r 14-1.2.1.1.1 16-1.2.1.1 17-1.2.1 19-1.2.2.2 20-1.2.2.2.1.r 21-1.2.2.2.1.1.1.1 22-1.2.2.2.1 23-1.2.2.2.1.2.1.1.1.1 24-1.2.2.2.1.1.1 24-1.2.2.2.1.2.1 25-1.2.2.2.1.1 25-1.2.2.2.1.2 27-1.3.1.1 27-1.3.1.2 30-1.3.1.1.1 32-1.3.1 34-1.3.1.2.1
(r / result-01~e.4
:ARG1 (o / overexpress-01~e.3
:ARG1 (p / protein
:name (n / name :op1 "HIF-1α785"~e.0,2)))
:ARG2~e.5 (i2 / increase-01~e.12
:ARG1~e.13 (g / grow-01~e.17
:ARG0-of (d / depend-01~e.16
:ARG1 (a / anchorage~e.14)))
:mod (s / small~e.7
:ARG1-of (c / contrast-01~e.9
:ARG2 (s2 / significant-02~e.11
:mod (s3 / statistics~e.10)))
:ARG1-of (r2 / relative-05~e.19
:ARG3~e.20 (o2 / or~e.22
:op1 (c4 / cell~e.25
:ARG1-of (t2 / transfect-01~e.24
:mod (m / mock~e.21)))
:op2 (c2 / cell~e.25
:ARG1-of (t / transfect-01~e.24
:ARG2 (p2 / protein
:name (n3 / name :op1 "lacz"~e.23))))))))
:ARG1-of (d2 / describe-01
:ARG0 (a2 / and~e.32
:op1 (f / figure~e.27 :mod "4C"~e.30)
:op2 (f2 / figure~e.27 :mod "4D"~e.34))))
# ::id pmid_1991_9690.71 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In contrast overexpression of both HIF @-@ 1αFL and HIF-α785 in SbCl2 resulted in a large and significant 3 @-@ fold increase in Matrigel invasion relative to mock or Lacz transfected cells ( Fig . 4B ) .
# ::alignments 1-1 2-1.1.1 5-1.1.1.1.1.1.1 5-1.1.1.1.2.1.1 8-1.1.1.1 10-1.1.1.2.r 11-1.1.1.2.1.1 12-1.1 13-1.1.2.r 15-1.1.2.3 17-1.1.2.4 18-1.1.2.2.1 20-1.1.2.2 21-1.1.2 22-1.1.2.1.r 23-1.1.2.1.1.1.1 24-1.1.2.1 25-1.1.2.5 26-1.1.2.5.1.r 27-1.1.2.5.1.2.1.1 28-1.1.2.5.1.2 29-1.1.2.5.1.2.2.1.1 30-1.1.2.5.1 31-1.1.2.5.1.1 33-1.2.1 36-1.2.1.1
(c / contrast-01~e.1
:ARG2 (r / result-01~e.12
:ARG1 (o / overexpress-01~e.2
:ARG1 (a / and~e.8
:op1 (p / protein
:name (n / name :op1 "HIF-1α"~e.5)
:ARG1-of (l4 / long-03
:degree (f / full)))
:op2 (p2 / protein
:name (n2 / name :op1 "HIF-1α785"~e.5)))
:location~e.10 (c2 / cell-line
:name (n3 / name :op1 "SbCl2"~e.11)))
:ARG2~e.13 (i / increase-01~e.21
:ARG1~e.22 (i2 / invade-01~e.24
:ARG0 (p4 / protein
:name (n4 / name :op1 "matrigel"~e.23)))
:ARG2 (p3 / product-of~e.20 :op1 3~e.18)
:mod (l3 / large~e.15)
:ARG1-of (s / significant-02~e.17)
:ARG1-of (r2 / relative-05~e.25
:ARG3~e.26 (t2 / transfect-01~e.30
:ARG1 (c5 / cell~e.31)
:ARG2 (o3 / or~e.28
:op1 (v / vector
:mod (m / mock~e.27))
:op2 (p5 / protein
:name (n6 / name :op1 "lacz"~e.29)))))))
:ARG1-of (d / describe-01
:ARG0 (f2 / figure~e.33 :mod "4B"~e.36)))
# ::id pmid_1991_9690.72 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok HIF @-@ 1α loss @-@ of @-@ function in human metastatic melanoma WM9 cells
# ::alignments 1-1.1.1.1 3-1.1.1.1 4-1 4-1.1.2 8-1.2 9-1.3.r 10-1.3.2 11-1.3.4 12-1.3.3.1.1 13-1.3.1.1 14-1.3
(l2 / lose-02~e.4
:ARG0 (p / protein
:name (n / name :op1 "HIF-1α"~e.1,3)
:mod (l / lose-01~e.4))
:ARG1 (f / function-01~e.8)
:location~e.9 (c / cell-line~e.14
:name (n2 / name :op1 "WM9"~e.13)
:mod (h / human~e.10)
:mod (m / medical-condition
:name (n3 / name :op1 "melanoma"~e.12))
:ARG1-of (m2 / metastasize-101~e.11)))
# ::id pmid_1991_9690.73 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok HIF @-@ 1α protein is highly expressed under normoxic conditions in the WM9 human metastatic melanoma cell line .
# ::alignments 0-1.1.1.1 2-1.1.1.1 3-1.1 5-1.4 6-1 9-1.3 10-1.2.r 12-1.2.1.1 13-1.2.2 14-1.2.4 15-1.2.3.1.1 16-1.2 17-1.2
(e / express-03~e.6
:ARG2 (p / protein~e.3
:name (n / name :op1 "HIF-1α"~e.0,2))
:ARG3~e.10 (c / cell-line~e.16,17
:name (n2 / name :op1 "WM9"~e.12)
:mod (h / human~e.13)
:mod (m / medical-condition
:name (n3 / name :op1 "melanoma"~e.15))
:ARG1-of (m2 / metastasize-101~e.14))
:ARG1-of (c2 / condition-01~e.9
:ARG2 (n4 / normoxia))
:ARG1-of (h2 / high-02~e.5))
# ::id pmid_1991_9690.74 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To determine whether HIF @-@ 1α could be contributing to the malignant characteristics of these cells , we knocked down its expression and examine how this affected anchorage independent growth and Matrigel invasion .
# ::alignments 1-1.3 2-1.3.2.1 2-1.3.2.1.r 3-1.1.2.1.1.1 5-1.1.2.1.1.1 6-1.3.2 8-1.3.2.2 9-1.3.2.2.2.r 11-1.3.2.2.2.2 12-1.3.2.2.2 13-1.3.2.2.2.1.r 14-1.3.2.2.2.1.1 15-1.3.2.2.2.1 17-1.1.1 18-1.1 19-1.1 21-1.1.2 22-1 23-1.2 24-1.2.2.1.r 25-1.3.2.2.2.1.1 26-1.2.2.1 27-1.2.2.1.2.1.1.2 28-1.2.2.1.2.1.1 28-1.2.2.1.2.1.1.1 28-1.2.2.1.2.1.1.1.r 29-1.2.2.1.2.1 30-1.2.2.1.2 31-1.2.2.1.2.2.1.1.1 32-1.2.2.1.2.2
(a / and~e.22
:op1 (k / knock-down-02~e.18,19
:ARG0 (w / we~e.17)
:ARG1 (e / express-03~e.21
:ARG2 (p2 / protein
:name (n / name :op1 "HIF-1α"~e.3,5))))
:op2 (e2 / examine-01~e.23
:ARG0 w
:ARG1 (t2 / thing
:manner-of~e.24 (a2 / affect-01~e.26
:ARG0 k
:ARG1 (a3 / and~e.30
:op1 (g / grow-01~e.29
:ARG0-of (d / depend-01~e.28 :polarity~e.28 -~e.28
:ARG1 (a4 / anchorage~e.27)))
:op2 (i / invade-01~e.32
:ARG0 (p3 / protein
:name (n2 / name :op1 "matrigel"~e.31)))))))
:purpose (d2 / determine-01~e.1
:ARG0 w
:ARG1 (p / possible-01~e.6 :mode~e.2 interrogative~e.2
:ARG1 (c / contribute-01~e.8
:ARG0 p2
:ARG1~e.9 (c2 / characteristic-02~e.12
:ARG1~e.13 (c3 / cell~e.15
:mod (t / this~e.14,25))
:ARG2 (m / malignant-02~e.11))))))
# ::id pmid_1991_9690.75 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok WM9 cells were treated with 100 nM siRNA targeting HIF @-@ 1α ( Dharmacon ) which consistently decreased its expression by ~ 75 @-@ 85 % ( Fig . 5A ) .
# ::alignments 0-1.1.1.1 1-1.1 3-1 4-1.2.r 5-1.2.3.1 6-1.2.3.2 7-1.2.1.1 8-1.2.2 9-1.2.2.1.1.1 11-1.2.2.1.1.1 13-1.2.4.1.1 16-1.3.3 17-1.3 18-1.3.1.1 18-1.3.1.1.r 19-1.3.1 20-1.3.2.r 21-1.3.2 22-1.3.2.1.1.1 24-1.3.2.1.2.1 25-1.3.2.1.1 25-1.3.2.1.2 27-1.4.1 30-1.4.1.1
(t / treat-04~e.3
:ARG1 (c / cell-line~e.1
:name (n / name :op1 "WM9"~e.0))
:ARG2~e.4 (n5 / nucleic-acid
:name (n2 / name :op1 "siRNA"~e.7)
:ARG0-of (t2 / target-01~e.8
:ARG1 (p / protein
:name (n3 / name :op1 "HIF-1α"~e.9,11)))
:quant (c2 / concentration-quantity :quant 100~e.5
:unit (n4 / nanomolar~e.6))
:source (c4 / company
:name (n6 / name :op1 "Dharmacon"~e.13)))
:ARG0-of (d / decrease-01~e.17
:ARG1 (e / express-03~e.19
:ARG2~e.18 p~e.18)
:ARG2~e.20 (a / approximately~e.21
:op1 (v / value-interval
:op1 (p2 / percentage-entity~e.25 :value 75~e.22)
:op2 (p3 / percentage-entity~e.25 :value 85~e.24)))
:manner (c3 / consistent-02~e.16))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.27 :mod "5A"~e.30)))
# ::id pmid_1991_9690.76 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Colony formation after 5 days in soft agarose was inhibited by 70 % in HIF @-@ 1α-siRNA transfected WM9 cells in comparison to cells transfected with control siRNA ( Fig . 5B ) .
# ::alignments 0-1.1.1 1-1.1 2-1.1.2 3-1.1.2.1.1 4-1.1.2.1.2 5-1.1.3.r 6-1.1.3.1 7-1.1.3 9-1 10-1.2.r 11-1.2.1 12-1.2 13-1.3.r 14-1.3.2.1.2.1.1.1 17-1.3.2 18-1.3.1.1 19-1.3 21-1.4.r 23-1.4 24-1.4.1 25-1.4.1.1.r 26-1.4.1.1.2 27-1.3.2.1.1.1 27-1.4.1.1.1.1 29-1.5.1 32-1.5.1.1
(i / inhibit-01~e.9
:ARG1 (f / form-01~e.1
:ARG1 (c / colony~e.0)
:time (a / after~e.2
:quant (t2 / temporal-quantity :quant 5~e.3
:unit (d2 / day~e.4)))
:location~e.5 (a2 / agarose~e.7
:ARG1-of (s / soft-02~e.6)))
:quant~e.10 (p / percentage-entity~e.12 :value 70~e.11)
:location~e.13 (c2 / cell-line~e.19
:name (n2 / name :op1 "WM9"~e.18)
:ARG1-of (t3 / transfect-01~e.17
:ARG2 (n6 / nucleic-acid
:name (n3 / name :op1 "siRNA"~e.27)
:ARG0-of (e / encode-01
:ARG1 (p2 / protein
:name (n4 / name :op1 "HIF-1α"~e.14))))))
:compared-to~e.21 (c3 / cell~e.23
:ARG1-of (t4 / transfect-01~e.24
:ARG2~e.25 (n7 / nucleic-acid
:name (n5 / name :op1 "siRNA"~e.27)
:mod (c4 / control~e.26))))
:ARG1-of (d3 / describe-01
:ARG0 (f2 / figure~e.29 :mod "5B"~e.32)))
# ::id pmid_1991_9690.77 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok A photo ( Fig . 5C ) of the colonies formed at this time point in control vs. HIF @-@ 1α transfected cells verifies this decrease in soft agar colony formation .
# ::alignments 1-1.1 3-1.1.2.1 6-1.1.2.1.1 9-1.1.1.r 11-1.1.1 12-1.1.1.1 14-1.2.2 15-1.1.1.1.1.r 16-1.1.1.1.1 17-1.1.1.1.2.r 18-1.1.1.1.2.2.1 19-1.1.1.1.2 20-1.1.1.1.2.1.1.1.1.1 22-1.1.1.1.2.1.1.1.1.1 23-1.1.1.1.2.1.1 23-1.1.1.1.2.2.2 24-1.1.1.1.2.1 24-1.1.1.1.2.2 25-1 26-1.2.2 27-1.2 28-1.2.1.r 29-1.2.1.1.1.1 30-1.2.1.1.1 31-1.2.1.1 32-1.2.1
(v / verify-01~e.25
:ARG0 (p / photograph-01~e.1
:ARG1~e.9 (c / colony~e.11
:ARG1-of (f / form-01~e.12
:time~e.15 (p2 / point~e.16)
:location~e.17 (c2 / contrast-01~e.19
:ARG1 (c3 / cell~e.24
:ARG1-of (t / transfect-01~e.23
:ARG2 (p3 / protein
:name (n / name :op1 "HIF-1α"~e.20,22))))
:ARG2 (c4 / cell~e.24
:mod (c5 / control~e.18)
:ARG1-of (t2 / transfect-01~e.23)))))
:ARG1-of (d2 / describe-01
:ARG0 (f3 / figure~e.3 :mod "5C"~e.6)))
:ARG1 (d / decrease-01~e.27
:ARG1~e.28 (f2 / form-01~e.32
:ARG1 (c6 / colony~e.31
:location (a / agar~e.30
:ARG1-of (s / soft-02~e.29))))
:mod (t3 / this~e.14,26)))
# ::id pmid_1991_9690.78 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Matrigel invasion was also significantly decreased in HIF @-@ 1α-siRNA transfected WM9 cells compared to control siRNA transfected WM9 cells ( Fig . 5D ) .
# ::alignments 0-1.1.1.1.1 1-1.1 3-1.2 4-1.3 5-1 6-1.4.r 7-1.4.2.1.2.1.1.1 10-1.4.2 10-1.5.2 11-1.4.1.1 11-1.5.1.1 12-1.4 12-1.5 13-1.5.r 14-1.5.2.1.r 15-1.5.2.1.2 16-1.4.2.1.1.1 16-1.5.2.1.1.1 17-1.4.2 18-1.4.1.1 19-1.4 21-1.6.1 24-1.6.1.1
(d / decrease-01~e.5
:ARG1 (i / invade-01~e.1
:ARG0 (p / protein
:name (n / name :op1 "matrigel"~e.0)))
:mod (a / also~e.3)
:ARG1-of (s / significant-02~e.4)
:location~e.6 (c / cell-line~e.12,19
:name (n2 / name :op1 "WM9"~e.11,18)
:ARG1-of (t / transfect-01~e.10,17
:ARG2 (n7 / nucleic-acid
:name (n3 / name :op1 "siRNA"~e.16)
:ARG0-of (e / encode-01
:ARG1 (p2 / protein
:name (n4 / name :op1 "HIF-1α"~e.7))))))
:compared-to~e.13 (c2 / cell-line~e.12
:name (n5 / name :op1 "WM9"~e.11)
:ARG1-of (t2 / transfect-01~e.10
:ARG2~e.14 (n8 / nucleic-acid
:name (n6 / name :op1 "siRNA"~e.16)
:mod (c3 / control~e.15))))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.21 :mod "5D"~e.24)))
# ::id pmid_1991_9690.79 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Measurement of cell viability in the Matrigel chambers shows no difference between control vs. HIF @-@ 1α siRNA transfected cells ( Fig . 5E ) .
# ::alignments 0-1.1 2-1.1.1.1 2-1.2.2 4-1.1.2.r 6-1.1.2.1.1.1 7-1.1.2 8-1 9-1.2.1 9-1.2.1.r 10-1.2 10-1.2.1 10-1.2.1.r 12-1.2.2.1.1.2 14-1.2.3.1.1.2.1.1.1 16-1.2.3.1.1.2.1.1.1 17-1.2.2.1.1.1.1 17-1.2.3.1.1.1.1 18-1.2.2.1 18-1.2.3.1 19-1.1.1.1 19-1.2.3 21-1.3.1 24-1.3.1.1
(s / show-01~e.8
:ARG0 (m / measure-01~e.0
:ARG1 (v / viable
:domain (c / cell~e.2,19))
:location~e.4 (c2 / chamber~e.7
:mod (p / protein
:name (n / name :op1 "matrigel"~e.6))))
:ARG1 (d / differ-02~e.10 :polarity~e.9,10 -~e.9,10
:ARG1 (c4 / cell~e.2
:ARG1-of (t / transfect-01~e.18
:ARG2 (n5 / nucleic-acid
:name (n2 / name :op1 "siRNA"~e.17)
:mod (c5 / control~e.12))))
:ARG2 (c6 / cell~e.19
:ARG1-of (t2 / transfect-01~e.18
:ARG2 (n6 / nucleic-acid
:name (n3 / name :op1 "siRNA"~e.17)
:ARG0-of (e / encode-01
:ARG1 (p2 / protein
:name (n4 / name :op1 "HIF-1α"~e.14,16)))))))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.21 :mod "5E"~e.24)))
# ::id pmid_1991_9690.80 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok These knock down studies suggest that increased non @-@ hypoxic expression of HIF @-@ 1α plays an important role in key malignant properties exhibited by these human melanoma cells .
# ::alignments 0-1.1.2 1-1.1.1 2-1.1.1 3-1.1 4-1 5-1.2.r 6-1.2.1.3 7-1.2.1.2.1 7-1.2.1.2.1.r 9-1.2.1.2 10-1.2.1 11-1.2.1.1.r 12-1.2.1.1.2.1 14-1.2.1.1.2.1 15-1.2 17-1.2.2.1 18-1.2.2 19-1.2.2.2.r 20-1.2.2.2.2 21-1.2.2.2.1 22-1.2.2.2 23-1.2.2.2.3 24-1.2.2.2.3.1.r 25-1.2.2.2.3.1.3 26-1.2.2.2.3.1.2 27-1.2.2.2.3.1.1.2.1 28-1.2.2.2.3.1
(s / suggest-01~e.4
:ARG0 (s2 / study-01~e.3
:ARG1 (k / knock-down-02~e.1,2)
:mod (t / this~e.0))
:ARG1~e.5 (p / play-02~e.15
:ARG0 (e / express-03~e.10
:ARG2~e.11 (p2 / protein :wiki "HIF1A"
:name (n / name :op1 "HIF-1α"~e.12,14))
:mod (h / hypoxic~e.9 :polarity~e.7 -~e.7)
:ARG1-of (i / increase-01~e.6))
:ARG1 (r / role~e.18
:mod (i2 / important~e.17)
:topic~e.19 (p3 / property~e.22
:ARG1-of (m / malignant-02~e.21)
:ARG1-of (k2 / key-02~e.20)
:ARG1-of (e2 / exhibit-01~e.23
:ARG0~e.24 (c / cell~e.28
:mod (m2 / medical-condition :wiki "Melanoma"
:name (n2 / name :op1 "melanoma"~e.27))
:mod (h2 / human~e.26)
:mod (t2 / this~e.25)))))))
# ::id pmid_1991_9690.81 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Regulation of HIF @-@ 1α expression in human melanoma by the ERK1 @/@ 2 MAPK pathway
# ::alignments 1-1 2-1.2.r 3-1.2.1.1.1 5-1.2.1.1.1 6-1.2 7-1.2.2.r 8-1.2.2.2 9-1.2.2.1.1 10-1.1.r 12-1.1.1.1 14-1.1.1.1 15-1.1.1.2 16-1.1
(r / regulate-01~e.1
:ARG0~e.10 (p2 / pathway~e.16
:name (n2 / name :op1 "ERK1/2"~e.12,14 :op2 "MAPK"~e.15))
:ARG1~e.2 (e / express-03~e.6
:ARG2 (p3 / protein
:name (n3 / name :op1 "HIF-1α"~e.3,5))
:ARG3~e.7 (m / medical-condition
:name (n4 / name :op1 "melanoma"~e.9)
:mod (h / human~e.8))))
# ::id pmid_1991_9690.82 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Hypoxia independent expression of HIF @-@ 1α is thought to be regulated by growth signaling pathways [ @ 18 , 19 @ ] and the majority of melanomas have constitutively active ERK1 @/@ 2 MAPK pathway due to BRAF or N @-@ Ras mutations [ @ 14 , 15 @ ] .
# ::alignments 0-1.1.1.2.2.2 1-1.1.1.2.2 1-1.1.1.2.2.1 1-1.1.1.2.2.1.r 2-1.1.1.2 3-1.1.1.2.1.r 4-1.1.1.2.1.1.1 6-1.1.1.2.1.1.1 8-1.1 11-1.1.1 12-1.1.1.1.r 13-1.1.1.1.1.1 14-1.1.1.1.1 15-1.1.1.1 18-1.1.2.1.1.1.1 22-1.1.2.1.1.1.2 25-1 25-1.1.2.1.1.1 27-1.2.1.2 28-1.2.1.2.r 29-1.2.1.1.1 29-1.2.1.3.1.1.1 30-1.2 31-1.2.2.2 32-1.2.2.4 33-1.2.2.1.1 35-1.2.2.1.1 36-1.2.2.1.2 37-1.2.2 38-1.2.2.3 39-1.2.2.3 40-1.2.2.3.1.1.1.1.1 41-1.2.2.3.1 42-1.2.2.3.1.2.1.1.1 44-1.2.2.3.1.2.1.1.1 45-1.2.2.3.1.1 45-1.2.2.3.1.2 48-1.2.3.1.1.1.1 52-1.2.3.1.1.1.2
(a2 / and~e.25
:op1 (t / think-01~e.8
:ARG1 (r / regulate-01~e.11
:ARG0~e.12 (p3 / pathway~e.15
:ARG0-of (s / signal-07~e.14
:ARG1 (g / grow-01~e.13)))
:ARG1 (e / express-03~e.2
:ARG2~e.3 (p2 / protein
:name (n2 / name :op1 "HIF-1α"~e.4,6))
:ARG0-of (d / depend-01~e.1 :polarity~e.1 -~e.1
:ARG1 (h / hypoxia~e.0))))
:ARG1-of (d2 / describe-01
:ARG0 (p4 / publication
:ARG1-of (c / cite-01
:ARG2 (a / and~e.25 :op1 18~e.18 :op2 19~e.22)))))
:op2 (h2 / have-03~e.30
:ARG0 (m4 / medical-condition
:name (n3 / name :op1 "melanoma"~e.29)
:quant~e.28 (m / majority~e.27)
:ARG1-of (i / include-91
:ARG2 (m5 / medical-condition
:name (n4 / name :op1 "melanoma"~e.29))))
:ARG1 (p5 / pathway~e.37
:name (n5 / name :op1 "ERK1/2"~e.33,35 :op2 "MAPK"~e.36)
:mod (c2 / constitutive~e.31)
:ARG1-of (c3 / cause-01~e.38,39
:ARG0 (o / or~e.41
:op1 (m2 / mutate-01~e.45
:ARG1 (e2 / enzyme
:name (n6 / name :op1 "BRAF"~e.40)))
:op2 (m3 / mutate-01~e.45
:ARG1 (e3 / enzyme
:name (n7 / name :op1 "N-Ras"~e.42,44)))))
:ARG0-of (a5 / activity-06~e.32))
:ARG1-of (d5 / describe-01
:ARG0 (p6 / publication
:ARG1-of (c4 / cite-01
:ARG2 (a4 / and :op1 14~e.48 :op2 15~e.52))))))
# ::id pmid_1991_9690.83 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Therefore , we determined whether HIF @-@ 1α expression in human metastatic melanoma WM9 cells was dependent on activation of ERK1 @/@ 2 MAPK signaling .
# ::alignments 0-1 2-1.1.1 3-1.1 4-1.1.2.1 4-1.1.2.1.r 5-1.1.2.2.1.1.1 7-1.1.2.2.1.1.1 8-1.1.2.2 9-1.1.2.2.2.r 10-1.1.2.2.2.3 11-1.1.2.2.2.4 12-1.1.2.2.2.2.1.1 13-1.1.2.2.2.1.1 14-1.1.2.2.2 16-1.1.2 17-1.1.2.3.r 18-1.1.2.3 19-1.1.2.3.1.r 20-1.1.2.3.1.1.1.1 22-1.1.2.3.1.1.1.1 23-1.1.2.3.1.1.1.2 24-1.1.2.3.1
(c / cause-01~e.0
:ARG1 (d / determine-01~e.3
:ARG0 (w / we~e.2)
:ARG1 (d2 / depend-01~e.16 :mode~e.4 interrogative~e.4
:ARG0 (e / express-03~e.8
:ARG2 (p2 / protein
:name (n2 / name :op1 "HIF-1α"~e.5,7))
:ARG3~e.9 (c2 / cell-line~e.14
:name (n3 / name :op1 "WM9"~e.13)
:mod (m / medical-condition
:name (n4 / name :op1 "melanoma"~e.12))
:mod (h / human~e.10)
:ARG1-of (m2 / metastasize-101~e.11)))
:ARG1~e.17 (a / activate-01~e.18
:ARG1~e.19 (s / signal-07~e.24
:ARG0 (p3 / pathway
:name (n5 / name :op1 "ERK1/2"~e.20,22 :op2 "MAPK"~e.23)))))))
# ::id pmid_1991_9690.84 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok These cells have an active ERK1 @/@ 2 MAPK pathway as evidenced by the high phosphorylation of ERK ( Fig . 6A ) .
# ::alignments 0-1.1.1 1-1.1 2-1 4-1.2.2 5-1.2.1.1 7-1.2.1.1 8-1.2.1.2 9-1.2 10-1.3.r 11-1.3 12-1.3.1.r 14-1.3.1.2 15-1.3.1 16-1.3.1.1.r 17-1.3.1.1.1.1 19-1.4.1 22-1.4.1.1
(h / have-03~e.2
:ARG0 (c / cell~e.1
:mod (t / this~e.0))
:ARG1 (p4 / pathway~e.9
:name (n3 / name :op1 "ERK1/2"~e.5,7 :op2 "MAPK"~e.8)
:ARG0-of (a2 / activity-06~e.4))
:ARG1-of~e.10 (e / evidence-01~e.11
:ARG0~e.12 (p2 / phosphorylate-01~e.15
:ARG1~e.16 (e2 / enzyme
:name (n2 / name :op1 "ERK"~e.17))
:ARG1-of (h2 / high-02~e.14)))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.19 :mod "6A"~e.22)))
# ::id pmid_1991_9690.85 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Treatment of WM9 cells with 30 μM U0126 , a selective U0126 MEK inhibitor , decreased ERK1 @/@ 2 phosphorylation and led to a time @-@ dependent decrease in HIF @-@ 1α protein expression ( Fig . 6A ) .
# ::alignments 0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.1.1 3-1.1.1.1 4-1.1.1.2.r 5-1.1.1.2.2.1 6-1.1.1.2.2.2 7-1.1.1.2.1.1 7-1.1.1.2.3.1.1.1 11-1.1.1.2.1.1 11-1.1.1.2.3.1.1.1 12-1.1.1.2.3.1.2.1.1.1 13-1.1.1.2.3.1 13-1.1.1.2.3.1.2 13-1.1.1.2.3.1.2.r 15-1.1 16-1.1.2.1.1.1 18-1.1.2.1.1.1 19-1.1.2 20-1 21-1.2 24-1.2.2.2.1 26-1.2.2.2 27-1.2.2 28-1.2.2.1.r 29-1.2.2.1.1.1.1 31-1.2.2.1.1.1.1 32-1.1.1.2.3.1.2.1 32-1.2.2.1.1 33-1.2.2.1 35-1.3.1 38-1.3.1.1
(a / and~e.20
:op1 (d / decrease-01~e.15
:ARG0 (t2 / treat-04~e.0
:ARG1~e.1 (c / cell-line~e.3
:name (n3 / name :op1 "WM9"~e.2))
:ARG2~e.4 (s2 / small-molecule
:name (n4 / name :op1 "U0126"~e.7,11)
:quant (c2 / concentration-quantity :quant 30~e.5
:unit (m / micromolar~e.6))
:ARG1-of (m2 / mean-01
:ARG2 (s3 / small-molecule~e.13
:name (n5 / name :op1 "U0126"~e.7,11)
:ARG0-of~e.13 (i / inhibit-01~e.13
:ARG1 (p / protein-family~e.32
:name (n2 / name :op1 "MEK"~e.12)))
:ARG0-of (s / select-01)))))
:ARG1 (p2 / phosphorylate-01~e.19
:ARG1 (e / enzyme
:name (n6 / name :op1 "ERK1/2"~e.16,18))))
:op2 (l / lead-03~e.21
:ARG1 t2
:ARG2 (d2 / decrease-01~e.27
:ARG1~e.28 (e2 / express-03~e.33
:ARG2 (p3 / protein~e.32
:name (n7 / name :op1 "HIF-1α"~e.29,31)))
:ARG0-of (d3 / depend-01~e.26
:ARG1 (t3 / time~e.24))))
:ARG1-of (d4 / describe-01
:ARG0 (f / figure~e.35 :mod "6A"~e.38)))
# ::id pmid_1991_9690.86 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Although 30 μM U0126 has been used in published studies to selectively inhibit MEK [ @ 16 , 21 @ ] , the original paper describing this inhibitor [ @ 22 @ ] used much lower concentrations to achieve high selectivity .
# ::alignments 0-1 1-1.2.1.2.1 2-1.2.1.2.2 3-1.2.1.1.1 6-1.2 8-1.1.1.2.2.1 8-1.2.3.1 8-1.2.4.1 9-1.2.4 12-1.2.2 13-1.2.2.2.1.1 16-1.2.3.1.1.1.1 20-1.2.3.1.1.1.2 25-1.1.1.1 26-1.1.1 27-1.1.1.2 27-1.1.1.2.2 27-1.1.1.2.2.r 27-1.2.3 29-1.2.2 32-1.1.1.2.2.1.1.1 35-1.1 36-1.1.2.1.1.1 37-1.1.2.1 37-1.1.2.1.1 37-1.1.2.1.1.r 38-1.1.2 38-1.2.1.2 40-1.1.3 41-1.1.3.2.1
(h / have-concession-91~e.0
:ARG1 (u2 / use-01~e.35
:ARG0 (p4 / paper~e.26
:mod (o / original~e.25)
:ARG0-of (d2 / describe-01~e.27
:ARG1 s
:ARG1-of~e.27 (d3 / describe-01~e.27
:ARG0 (p5 / publication~e.8
:ARG1-of (c3 / cite-01 :ARG2 22~e.32)))))
:ARG1 (c4 / concentrate-02~e.38
:ARG1-of (l / low-04~e.37
:degree~e.37 (m / more~e.37
:degree (m3 / much~e.36))))
:ARG2 (a2 / achieve-01~e.40
:ARG0 p4
:ARG1 (s4 / select-01
:ARG1-of (h2 / high-02~e.41))))
:ARG2 (u / use-01~e.6
:ARG1 (s / small-molecule
:name (n / name :op1 "U0126"~e.3)
:quant (c / concentration-quantity~e.38 :quant 30~e.1
:unit (m2 / micromolar~e.2)))
:ARG2 (i2 / inhibit-01~e.12,29
:ARG0 s
:ARG1 (e / enzyme
:name (n2 / name :op1 "MEK"~e.13))
:ARG0-of (s5 / select-01))
:ARG1-of (d / describe-01~e.27
:ARG0 (p3 / publication~e.8
:ARG1-of (c2 / cite-01
:ARG2 (a / and :op1 16~e.16 :op2 21~e.20))))
:location (s2 / study-01~e.9
:ARG1-of (p2 / publish-01~e.8))))
# ::id pmid_1991_9690.87 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Therefore we repeated this experiment using 10 μM U0126 ( Fig . 6B ) .
# ::alignments 0-1 1-1.1.1 2-1.1 3-1.1.2.1 4-1.1.2 5-1.1.3 6-1.1.3.2.2.1 7-1.1.3.2.2.2 8-1.1.3.2.1.1 10-1.2.1 13-1.2.1.1
(c / cause-01~e.0
:ARG1 (r / repeat-01~e.2
:ARG0 (w / we~e.1)
:ARG1 (e / experiment-01~e.4
:mod (t / this~e.3))
:manner (u / use-01~e.5
:ARG0 w
:ARG1 (s / small-molecule
:name (n / name :op1 "U0126"~e.8)
:quant (c2 / concentration-quantity :quant 10~e.6
:unit (m / micromolar~e.7)))))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.10 :mod "6B"~e.13)))
# ::id pmid_1991_9690.88 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok At 24 h of treatment , 10 μM U0126 completely suppressed the phosphorylation of ERK1 @/@ 2 , yet there was minimal change in the level of HIF @-@ 1α relative to control cells .
# ::alignments 1-1.5.2.1 2-1.5.2.2 4-1.5.1 6-1.1.2.1 7-1.1.2.2 8-1.1.1.1 9-1.3 10-1 12-1.2 13-1.2.1.r 14-1.2.1.1.1 16-1.2.1.1.1 21-1.4.1.2 25-1.4.1.1 26-1.4.1.1.1.r 27-1.4.1.1.1.1.1 29-1.4.1.1.1.1.1 30-1.4.1.3 31-1.4.1.3.1.r 32-1.4.1.3.1.1 33-1.4.1.3.1
(s2 / suppress-01~e.10
:ARG0 (s / small-molecule
:name (n / name :op1 "U0126"~e.8)
:quant (c / concentration-quantity :quant 10~e.6
:unit (m / micromolar~e.7)))
:ARG1 (p / phosphorylate-01~e.12
:ARG1~e.13 (e / enzyme
:name (n2 / name :op1 "ERK1/2"~e.14,16)))
:ARG1-of (c2 / complete-02~e.9)
:ARG1-of (c3 / contrast-01
:ARG2 (c4 / charge-03
:ARG1 (l / level~e.25
:quant-of~e.26 (p2 / protein
:name (n3 / name :op1 "HIF-1α"~e.27,29)))
:ARG1-of (m2 / minimal-02~e.21)
:ARG1-of (r / relative-05~e.30
:ARG3~e.31 (c5 / cell~e.33
:mod (c6 / control~e.32)))))
:time (a / after
:op1 (t / treat-04~e.4)
:quant (t2 / temporal-quantity :quant 24~e.1
:unit (h / hour~e.2))))
# ::id pmid_1991_9690.89 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok With further time of inhibitor treatment , phosphorylation of ERK was not totally suppressed , but HIF @-@ 1α levels decreased .
# ::alignments 1-1.4.1 2-1.4 3-1.4.2.r 4-1.4.2.1 4-1.4.2.1.1 4-1.4.2.1.1.r 5-1.4.2 7-1.1 8-1.1.1.r 9-1.1.1.1.1 11-1.3.1 11-1.3.1.r 12-1.3 13-1 15-1.2 16-1.2.1.1.1.1.1 18-1.2.1.1.1.1.1 19-1.2.1.1 20-1.2.1
(s / suppress-01~e.13
:ARG1 (p / phosphorylate-01~e.7
:ARG1~e.8 (e / enzyme
:name (n / name :op1 "ERK"~e.9)))
:ARG1-of (c / contrast-01~e.15
:ARG2 (d / decrease-01~e.20
:ARG1 (l / level~e.19
:quant-of (p3 / protein
:name (n2 / name :op1 "HIF-1α"~e.16,18)))))
:degree (t / total~e.12 :polarity~e.11 -~e.11)
:condition (t4 / time~e.2
:mod (f / further~e.1)
:duration-of~e.3 (t3 / treat-04~e.5
:ARG2 (s2 / small-molecule~e.4
:ARG0-of~e.4 (i / inhibit-01~e.4)))))
# ::id pmid_1991_9690.90 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok We also used siRNA specifically targeting MEK1 and 2 in WM9 cells to inhibit ERK1 @/@ 2 phosphorylation .
# ::alignments 0-1.1 1-1.4 2-1 3-1.3.1 4-1.3.1 5-1.3.1 6-1.3.1 7-1.3.1 8-1.3.2.1.1.1 9-1.2.r 10-1.2.2.2.1.1 11-1.2.2.2 13-1.3 14-1.3.2.1.1.1 16-1.3.2.1.1.1 17-1.3.2
(u / use-01~e.2
:ARG0 (w / we~e.0)
:ARG1~e.9 (n6 / nucleic-acid
:name (n / name :op1 "siRNA")
:ARG0-of (t / target-01
:ARG1 (a2 / and
:op1 (e / enzyme
:name (n2 / name :op1 "MEK1"))
:op2 (e2 / enzyme
:name (n3 / name :op1 "MEK2")))
:location (c / cell-line~e.11
:name (n4 / name :op1 "WM9"~e.10))
:manner (s / specific-02)))
:ARG2 (i / inhibit-01~e.13
:ARG0 n6~e.3,4,5,6,7
:ARG1 (p / phosphorylate-01~e.17
:ARG1 (e3 / enzyme
:name (n5 / name :op1 "ERK1/2"~e.8,14,16))))
:mod (a / also~e.1))
# ::id pmid_1991_9690.91 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Treatment of WM9 cells with siRNA targeting MEK1 and 2 consistently decreased its expression by greater than 90 % and also decreased ERK1 @/@ 2 phosphorylation .
# ::alignments 0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.1.1 3-1.1.1.1 4-1.1.1.2.r 5-1.1.1.2.1.1 6-1.1.1.2.2 7-1.1.1.2.2.1.1.1.1 8-1.1.1.2.2.1 9-1.2.2.1.1.1 10-1.1.4 11-1.1 12-1.1.2.1 12-1.1.2.1.r 13-1.1.2 16-1.1.3 17-1.1.3.1.1 18-1.1.3.1 19-1 20-1.2.3 21-1.2 22-1.2.2.1.1.1 24-1.2.2.1.1.1 25-1.2.2
(a / and~e.19
:op1 (d / decrease-01~e.11
:ARG0 (t / treat-04~e.0
:ARG1~e.1 (c / cell-line~e.3
:name (n / name :op1 "WM9"~e.2))
:ARG2~e.4 (n6 / nucleic-acid
:name (n2 / name :op1 "siRNA"~e.5)
:ARG0-of (t2 / target-01~e.6
:ARG1 (a2 / and~e.8
:op1 (e / enzyme
:name (n3 / name :op1 "MEK1"~e.7))
:op2 (e2 / enzyme
:name (n4 / name :op1 "MEK2"))))))
:ARG1 (e3 / express-03~e.13
:ARG3~e.12 c~e.12)
:ARG2 (m / more-than~e.16
:op1 (p / percentage-entity~e.18 :value 90~e.17))
:manner (c2 / consistent-02~e.10))
:op2 (d2 / decrease-01~e.21
:ARG0 t
:ARG1 (p2 / phosphorylate-01~e.25
:ARG1 (e4 / enzyme
:name (n5 / name :op1 "ERK1/2"~e.9,22,24)))
:mod (a3 / also~e.20)))
# ::id pmid_1991_9690.92 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok However , knockdown of MEK1 and 2 did not decrease the normoxic expression of HIF @-@ 1α protein in human metastatic melanoma WM9 cells ( Fig . 6C ) .
# ::alignments 0-1 2-1.1.2 3-1.1.2.1.r 4-1.1.2.1.1.1.1 5-1.1.2.1 8-1.1.1 8-1.1.1.r 9-1.1 12-1.1.3 13-1.1.3.1.r 14-1.1.3.1.1.1 16-1.1.3.1.1.1 17-1.1.3.1 18-1.1.3.2.r 19-1.1.3.2.3 20-1.1.3.2.4 21-1.1.3.2.2.1.1 22-1.1.3.2.1.1 23-1.1.3.2 25-1.2.1 28-1.2.1.1
(c / contrast-01~e.0
:ARG2 (d / decrease-01~e.9 :polarity~e.8 -~e.8
:ARG0 (k / knock-down-02~e.2
:ARG1~e.3 (a / and~e.5
:op1 (e / enzyme
:name (n / name :op1 "MEK1"~e.4))
:op2 (e2 / enzyme
:name (n2 / name :op1 "MEK2"))))
:ARG1 (e3 / express-03~e.12
:ARG2~e.13 (p / protein~e.17
:name (n4 / name :op1 "HIF-1α"~e.14,16))
:ARG3~e.18 (c2 / cell-line~e.23
:name (n5 / name :op1 "WM9"~e.22)
:mod (m / medical-condition
:name (n6 / name :op1 "melanoma"~e.21))
:mod (h / human~e.19)
:ARG1-of (m2 / metastasize-101~e.20))
:mod (n3 / normoxia)))
:ARG1-of (d3 / describe-01
:ARG0 (f / figure~e.25 :mod "6C"~e.28)))
# ::id pmid_2000_3375.1 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Aurora @-@ A overexpression enhances cell @-@ aggregation of Ha @- @ ras @ transformants through the MEK @/@ ERK signaling pathway ( PMID : 20003375 )
# ::alignments 0-1.1.1.1.1 2-1.1.1.1.1 3-1.1 4-1 5-1.2.1 7-1.2 9-1.2.1.1.1.1.1 12-1.2.1.1.1.1.1 14-1.2.1 14-1.2.1.1 14-1.2.1.1.r 17-1.3.1.1.1 19-1.3.1.1.1 20-1.3 21-1.3.1
(e / enhance-01~e.4
:ARG0 (o / overexpress-01~e.3
:ARG1 (e2 / enzyme
:name (n / name :op1 "Aurora-A"~e.0,2)))
:ARG1 (a / aggregate-01~e.7
:ARG1 (c3 / cell~e.5,14
:ARG2-of~e.14 (t / transform-01~e.14
:ARG0 (g / gene
:name (n2 / name :op1 "Ha-ras"~e.9,12)))))
:manner (s / signal-07~e.20
:ARG0 (p / pathway~e.21
:name (n3 / name :op1 "MEK/ERK"~e.17,19)))
:ARG1-of (d / describe-01
:ARG0 (p2 / publication-91 :ARG8 "PMID20003375")))
# ::id pmid_2000_3375.12 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Results
# ::alignments 1-1 1-1.1 1-1.1.r
(t / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1))
# ::id pmid_2000_3375.13 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Overexpression of wild @-@ type Aurora @-@ A and mutation of Ras @ V12 @ were detected in human bladder and colon cancer tissues .
# ::alignments 0-1.1.1 1-1.1.1.1.r 2-1.1.1.1.2 4-1.1.1.1.2 5-1.1.1.1.1.1 7-1.1.1.1.1.1 8-1.1 9-1.1.2 10-1.1.2.2.r 11-1.1.2.2.1.1 13-1.1.2.1 16-1 17-1.2.r 18-1.2.1.1 19-1.2.1.2.3 20-1.2 21-1.2.2.2.2.1 22-1.2.1.2.2.1 22-1.2.2.2.2.2 23-1.2.1 23-1.2.2
(d / detect-01~e.16
:ARG1 (a / and~e.8
:op1 (o / overexpress-01~e.0
:ARG1~e.1 (e / enzyme
:name (n / name :op1 "Aurora-A"~e.5,7)
:mod (w / wild-type~e.2,4)))
:op2 (m / mutate-01~e.9 :value "V12"~e.13
:ARG2~e.10 (e2 / enzyme
:name (n2 / name :op1 "Ras"~e.11))))
:location~e.17 (a3 / and~e.20
:op1 (t / tissue~e.23
:mod (h / human~e.18)
:mod (d4 / disease :wiki "Cancer"
:name (n5 / name :op1 "cancer"~e.22)
:mod (b / bladder~e.19)))
:op2 (t2 / tissue~e.23
:mod h
:mod (d2 / disease :wiki "Colorectal_cancer"
:name (n3 / name :op1 "colon"~e.21 :op2 "cancer"~e.22)))))
# ::id pmid_2000_3375.14 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Wild @-@ type Aurora @-@ A induces focus formation and aggregation of the Ras @ V12 @ transformants .
# ::alignments 0-1.1.2 2-1.1.2 3-1.1.1.1 5-1.1.1.1 6-1 7-1.2.1.1 8-1.2.1 9-1.2 10-1.2.2 11-1.2.2.1.r 13-1.2.2.1.1.1.1.1 15-1.2.2.1.1.1.2.1 17-1.2.2.1 17-1.2.2.1.1 17-1.2.2.1.1.r
(i / induce-01~e.6
:ARG0 (e / enzyme
:name (n / name :op1 "Aurora-A"~e.3,5)
:mod (w / wild-type~e.0,2))
:ARG2 (a / and~e.9
:op1 (f / form-01~e.8
:ARG1 (f2 / focus~e.7))
:op2 (a2 / aggregate-01~e.10
:ARG1~e.11 (c / cell~e.17
:ARG2-of~e.17 (t / transform-01~e.17
:ARG0 (e2 / enzyme
:name (n2 / name :op1 "Ras"~e.13)
:ARG2-of (m / mutate-01 :value "V12"~e.15)))))))
# ::id pmid_2000_3375.15 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Aurora @-@ A activates Ral A and the phosphorylation of AKT as well as enhances the phosphorylation of MEK , ERK of WT cells .
# ::alignments 0-1.1.1.1.1 2-1.1.1.1.1 3-1.1 4-1.1.2.1.1.1 5-1.1.2.1.1.2 6-1.1.2 8-1.1.2.2 9-1.1.2.2.1.r 10-1.1.2.2.1.1.1 11-1 12-1 13-1 14-1.2 16-1.2.2 17-1.2.2.1.r 18-1.2.2.1.1.1.1 20-1.2.2.1.2.1.1 22-1.2.2.1.3.1 23-1.2.2.1.3
(a / and~e.11,12,13
:op1 (a2 / activate-01~e.3
:ARG0 (e / enzyme
:name (n / name :op1 "Aurora-A"~e.0,2))
:ARG1 (a3 / and~e.6
:op1 (e5 / enzyme
:name (n2 / name :op1 "Ral"~e.4 :op2 "A"~e.5))
:op2 (p2 / phosphorylate-01~e.8
:ARG1~e.9 (e2 / enzyme
:name (n3 / name :op1 "AKT"~e.10)))))
:op2 (e3 / enhance-01~e.14
:ARG0 e
:ARG1 (p3 / phosphorylate-01~e.16
:ARG1~e.17 (a4 / and
:op1 (e4 / enzyme
:name (n4 / name :op1 "MEK"~e.18))
:op2 (e6 / enzyme
:name (n5 / name :op1 "ERK"~e.20))
:part-of (c / cell~e.23
:mod (w / wild-type~e.22))))))
# ::id pmid_2000_3375.16 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Finally , the Ras/MEK/ERK signaling pathway is responsible for Aurora @-@ A induced aggregation of the Ras @ V12 @ transformants .
# ::alignments 0-1.1 0-1.1.r 3-1.2.1.1 4-1.2.2 5-1.2 7-1 8-1.3.r 9-1.3.2.1.1.1 11-1.3.2.1.1.1 12-1.3.2 13-1.3 14-1.3.1.r 16-1.3.1.1.1.1.1 18-1.3.1.1.1.2.1 20-1.3.1 20-1.3.1.1 20-1.3.1.1.r
(r / responsible-01~e.7 :li~e.0 -1~e.0
:ARG0 (p / pathway~e.5
:name (n / name :op1 "Ras/MEK/ERK"~e.3)
:ARG0-of (s / signal-07~e.4))
:ARG1~e.8 (a / aggregate-01~e.13
:ARG1~e.14 (c / cell~e.20
:ARG1-of~e.20 (t / transform-01~e.20
:ARG0 (e2 / enzyme
:name (n3 / name :op1 "Ras"~e.16)
:ARG2-of (m / mutate-01 :value "V12"~e.18))))
:ARG2-of (i / induce-01~e.12
:ARG0 (e / enzyme
:name (n2 / name :op1 "Aurora-A"~e.9,11)))))
# ::id pmid_2000_3375.109 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Results
# ::alignments 1-1 1-1.1 1-1.1.r
(t / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1))
# ::id pmid_2000_3375.110 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Detection of Aurora @-@ A overexpression accompanied with Ha @- @ ras @ mutation in bladder cancers
# ::alignments 1-1 2-1.1.r 3-1.1.2.1.1.1 5-1.1.2.1.1.1 6-1.1.2 7-1.1 8-1.1.1.r 9-1.1.1.1.1.1 12-1.1.1.1.1.1 14-1.1.1 15-1.2.r 16-1.2.3 17-1.2.2.1
(d / detect-01~e.1
:ARG1~e.2 (a / accompany-01~e.7
:ARG0~e.8 (m / mutate-01~e.14
:ARG1 (g / gene
:name (n2 / name :op1 "Ha-ras"~e.9,12)))
:ARG1 (o / overexpress-01~e.6
:ARG1 (e / enzyme
:name (n / name :op1 "Aurora-A"~e.3,5))))
:location~e.15 (d2 / disease :wiki "Cancer"
:name (n3 / name :op1 "cancer"~e.17)
:mod (b / bladder~e.16)))
# ::id pmid_2000_3375.111 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Aurora @-@ A overexpression accompanied with Ha @- @ ras @ codon 12 mutation has been reported in bladder cancers [ @ 41 @ ] .
# ::alignments 0-1.1.2.1.1.1 2-1.1.2.1.1.1 3-1.1.2 4-1.1 5-1.1.1.r 6-1.1.1.1.2.1.1 9-1.1.1.1.2.1.1 11-1.1.1.1 12-1.1.1.1.1 13-1.1.1 16-1 17-1.1.3.r 18-1.1.3.3 19-1.1.3.2.1 22-1.2.1.1.1
(r / report-01~e.16
:ARG1 (a / accompany-01~e.4
:ARG0~e.5 (m / mutate-01~e.13
:ARG1 (c2 / codon~e.11 :mod 12~e.12
:part-of (g / gene
:name (n3 / name :op1 "Ha-ras"~e.6,9))))
:ARG1 (o / overexpress-01~e.3
:ARG1 (e / enzyme
:name (n / name :op1 "Aurora-A"~e.0,2)))
:location~e.17 (d / disease :wiki "Cancer"
:name (n4 / name :op1 "cancer"~e.19)
:mod (b / bladder~e.18)))
:ARG1-of (d2 / describe-01
:ARG0 (p / publication-91
:ARG1-of (c / cite-01 :ARG2 41~e.22))))
# ::id pmid_2000_3375.112 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In this study , Ha @- @ ras @ V12 @ mutation was detected in the tumour part of the bladder cancer specimen by SNP @-@ real @-@ time PCR and verified by sequence analysis ( Figure 1A , Gly12 -> Val 12 ) .
# ::alignments 1-1.3.1 2-1.3 4-1.1.1.2.1.1 7-1.1.1.2.1.1 10-1.1.1.1 12-1.1.1 12-1.4.2 14-1.1 15-1.1.3.r 17-1.1.3 18-1.1.3.1.r 21-1.1.3.1.1.3 22-1.1.3.1.1.2.1 23-1.1.3.1 27-1.1.2.2.1 29-1.1.2.2.1 30-1.1.2.2.2 30-1.1.2.2.2.1 30-1.1.2.2.2.1.r 31-1 32-1.2 34-1.2.2.1 35-1.1.2.2 35-1.2.2 37-1.4.1 39-1.4.1.1 45-1.4.2.1.1 45-1.4.2.2.1
(a2 / and~e.31
:op1 (d3 / detect-01~e.14
:ARG1 (m2 / mutate-01~e.12 :value "V12"~e.10
:ARG2 (e / enzyme
:name (n3 / name :op1 "Ha-ras"~e.4,7)))
:ARG2 (p / polymorphism
:mod (n2 / nucleotide
:ARG1-of (s / single-02))
:ARG1-of (a / analyze-01~e.35
:manner (r / real-time~e.27,29)
:mod (r2 / react-01~e.30
:ARG0~e.30 (p2 / polymerase~e.30)
:mod (c / chain)
:subevent (t / transcribe-01
:ARG1-of (r3 / reverse-01)))))
:location~e.15 (t2 / tumor~e.17
:part-of~e.18 (s2 / specimen~e.23
:mod (d4 / disease :wiki "Cancer"
:name (n4 / name :op1 "cancer"~e.22)
:mod (b2 / bladder~e.21)))))
:op2 (v / verify-01~e.32
:ARG1 m2
:manner (a3 / analyze-01~e.35
:mod (s3 / sequence~e.34)))
:medium (s4 / study-01~e.2
:mod (t3 / this~e.1))
:ARG1-of (d5 / describe-01
:ARG0 (f / figure~e.37 :mod "1A"~e.39)
:ARG2 (m3 / mutate-01~e.12
:ARG1 (a4 / amino-acid :mod 12~e.45
:name (n5 / name :op1 "glycine"))
:ARG2 (a5 / amino-acid :mod 12~e.45
:name (n6 / name :op1 "valine")))))
# ::id pmid_2000_3375.113 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The Aurora @-@ A protein overexpression was detected in the same cancer part of the bladder tissue compared to the normal part by IHC staining ( Figure 1B , T vs. N ) .
# ::alignments 1-1.1.1.1.1 3-1.1.1.1.1 5-1.1 7-1 8-1.4.r 10-1.4.3 11-1.4.4.2.1 12-1.4 13-1.4.1.r 15-1.4.1.1 16-1.4.1 17-1.4.2 20-1.4.2.1.1 21-1.4.2.1 24-1.2 26-1.3.1 28-1.3.1.1 32-1.4.2
(d / detect-01~e.7
:ARG1 (o / overexpress-01~e.5
:ARG1 (e / enzyme
:name (n / name :op1 "Aurora-A"~e.1,3)))
:manner (s2 / stain-01~e.24
:ARG2 (i / immunohistochemistry))
:ARG1-of (d3 / describe-01
:ARG0 (f2 / figure~e.26 :mod "1B"~e.28))
:location~e.8 (p2 / part~e.12
:part-of~e.13 (t / tissue~e.16
:mod (b / bladder~e.15))
:ARG1-of (c2 / compare-01~e.17,32
:ARG2 (p4 / part~e.21
:ARG1-of (n4 / normal-02~e.20)))
:ARG1-of (s / same-01~e.10)
:mod (d2 / disease :wiki "Cancer"
:name (n2 / name :op1 "cancer"~e.11))))
# ::id pmid_2000_3375.114 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Similarly , Ki @- @ ras @ codon 12 mutation and higher expression level of Aurora @-@ A were only detected in the cancer part of the colon tissue ( Figure 1C and 1D ) .
# ::alignments 0-1 2-1.1.1.1.1.2.1.1 5-1.1.1.1.1.2.1.1 7-1.1.1.1.1 8-1.1.1.1.1.1 9-1.1.1.1 10-1.1.1 11-1.1.1.2.2 11-1.1.1.2.2.1 11-1.1.1.2.2.1.r 12-1.1.1.2.1 13-1.1.1.2 14-1.1.1.2.1.1.r 15-1.1.1.2.1.1.1.1 17-1.1.1.2.1.1.1.1 19-1.1.3 20-1.1 21-1.1.2.r 23-1.1.2.1.2.1 24-1.1.2 25-1.1.2.2.r 27-1.1.2.2.1 28-1.1.2.2 30-1.1.4.1.1 30-1.1.4.1.2 32-1.1.4.1.1.1 34-1.1.4.1 36-1.1.4.1.2.1
(r / resemble-01~e.0
:ARG2 (d / detect-01~e.20
:ARG1 (a / and~e.10
:op1 (m / mutate-01~e.9
:ARG1 (c3 / codon~e.7 :mod 12~e.8
:part-of (g / gene
:name (n2 / name :op1 "Ki-ras"~e.2,5))))
:op2 (l / level~e.13
:degree-of (e / express-03~e.12
:ARG2~e.14 (e2 / enzyme
:name (n3 / name :op1 "Aurora-A"~e.15,17)))
:ARG1-of (h / high-02~e.11
:degree~e.11 (m2 / more~e.11))))
:location~e.21 (p / part~e.24
:mod (d2 / disease :wiki "Cancer"
:name (n4 / name :op1 "cancer"~e.23))
:part-of~e.25 (t / tissue~e.28
:mod (c2 / colon~e.27)))
:manner (o / only~e.19)
:ARG1-of (d3 / describe-01
:ARG0 (a3 / and~e.34
:op1 (f / figure~e.30 :mod "1C"~e.32)
:op2 (f2 / figure~e.30 :mod "1D"~e.36)))))
# ::id pmid_2000_3375.115 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Taken together , despite of the difference in transformation of NIH3T3 cells by Ki @- @ ras @ and Ha @- @ ras , overexpression of Aurora @-@ A and Ras @ V12 @ ( Ki @- or Ha-) mutations are simultaneously detected in various cancers including bladder and colon .
# ::alignments 0-1.1.3 1-1.1.3.1 3-1.3.r 6-1.3 7-1.3.3.r 8-1.3.3 9-1.3.3.1.r 10-1.3.3.1.1.1 11-1.3.3.1 13-1.1.2.2.1.1.1 19-1.1.2.2.2.1.1 25-1.1.1 26-1.1.1.1.r 27-1.1.1.1.1.1 29-1.1.1.1.1.1 30-1.1 31-1.1.2.2.1.1.1 31-1.1.2.2.2.1.1 33-1.1.2.1 36-1.1.2.2.1.1.1 38-1.1.2.2 40-1.1.2 42-1.2 42-1.2.r 43-1 44-1.4.r 45-1.4.3 46-1.4.2.1 46-1.4.4.1.1.2.1 46-1.4.4.1.2.2.2 47-1.4.4 48-1.4.4.1.1.3 49-1.4.4.1 50-1.4.4.1.2.2.1
(d / detect-01~e.43
:ARG1 (a / and~e.30
:op1 (o / overexpress-01~e.25
:ARG1~e.26 (e / enzyme
:name (n / name :op1 "Aurora-A"~e.27,29)))
:op2 (m / mutate-01~e.40 :value "V12"~e.33
:ARG1 (o2 / or~e.38
:op1 (e2 / enzyme
:name (n2 / name :op1 "Ki-Ras"~e.13,31,36))
:op2 (e3 / enzyme
:name (n3 / name :op1 "Ha-Ras"~e.19,31))))
:ARG1-of (t3 / take-01~e.0
:mod (t2 / together~e.1)))
:manner~e.42 (s / simultaneous~e.42)
:concession~e.3 (d2 / differ-02~e.6
:ARG1 e2
:ARG2 e3
:ARG3~e.7 (t / transform-01~e.8
:ARG1~e.9 (c / cell-line~e.11
:name (n4 / name :op1 "NIH3T3"~e.10))))
:location~e.44 (d6 / disease :wiki "Cancer"
:name (n5 / name :op1 "cancer"~e.46)
:mod (v / various~e.45)
:ARG1-of (i / include-91~e.47
:ARG2 (a2 / and~e.49
:op1 (d3 / disease :wiki "Cancer"
:name (n6 / name :op1 "cancer"~e.46)
:mod (b / bladder~e.48))
:op2 (d4 / disease :wiki "Colorectal_cancer"
:name (n7 / name :op1 "colon"~e.50 :op2 "cancer"~e.46))))))
# ::id pmid_2000_3375.116 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Establishment of stable cell lines over @-@ expressing Aurora @-@ A and mutant Ras @ V12 @
# ::alignments 1-1 2-1.1.r 3-1.1.1 4-1.1 5-1.1 9-1.1.2.1.1.1.1 11-1.1.2.1.1.1.1 12-1.1.2.1 13-1.1.2.1.2 13-1.1.2.1.2.2 13-1.1.2.1.2.2.r 14-1.1.2.1.2.1.1 16-1.1.2.1.2.2.1
(e / establish-01~e.1
:ARG1~e.2 (c / cell-line~e.4,5
:ARG1-of (s / stable-03~e.3)
:ARG0-of (o / overexpress-01
:ARG1 (a / and~e.12
:op1 (e2 / enzyme
:name (n / name :op1 "Aurora-A"~e.9,11))
:op2 (e3 / enzyme~e.13
:name (n2 / name :op1 "Ras"~e.14)
:ARG2-of~e.13 (m / mutate-01~e.13 :value "V12"~e.16))))))
# ::id pmid_2000_3375.117 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok It is intriguing to unravel the combined effects of Aurora @-@ A and mutant Ras @ V12 @ on the morphological change and tumorigenesis of the cells .
# ::alignments 2-1 4-1.1 6-1.1.1.3 7-1.1.1 8-1.1.1.1.r 9-1.1.1.1.1.1.1 11-1.1.1.1.1.1.1 12-1.1.1.1 13-1.1.1.1.2 13-1.1.1.1.2.2 13-1.1.1.1.2.2.r 14-1.1.1.1.2.1.1 16-1.1.1.1.2.2.1 18-1.1.1.2.r 20-1.1.1.2.1.2 21-1.1.1.2.1 22-1.1.1.2 23-1.1.1.2.2 23-1.1.1.2.2.1 23-1.1.1.2.2.1.r 24-1.1.1.2.2.1.1.r 26-1.1.1.2.2.1.1
(i / intrigue-01~e.2
:ARG0 (u / unravel-01~e.4
:ARG1 (a / affect-01~e.7
:ARG0~e.8 (a2 / and~e.12
:op1 (e / enzyme
:name (n / name :op1 "Aurora-A"~e.9,11))
:op2 (e2 / enzyme~e.13
:name (n2 / name :op1 "Ras"~e.14)
:ARG2-of~e.13 (m / mutate-01~e.13 :value "V12"~e.16)))
:ARG1~e.18 (a3 / and~e.22
:op1 (c2 / change-01~e.21
:ARG1 c3
:mod (m2 / morphology~e.20))
:op2 (c4 / create-01~e.23
:ARG1~e.23 (t / tumor~e.23
:mod~e.24 (c3 / cell~e.26))))
:ARG1-of (c / combine-01~e.6))))
# ::id pmid_2000_3375.118 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Stable cell lines were established by transfecting Vector DNA , wild @-@ type Aurora @-@ A or kinase @-@ inactivated Aurora @-@ A into 7 @-@ 4 cells , which was derived from NIH @/@ 3T3 cells harboring the inducible Ha @- @ ras @ V12 @ oncogene [ @ 23 @ ] , designated Vector , WT and KD cell line , respectively .
# ::alignments 0-1.1.1 1-1.1 2-1.1 4-1 7-1.2.2.1.3 8-1.2.2.1.2.1 10-1.2.2.2.2 12-1.2.2.2.2 13-1.2.2.2.1.1 13-1.2.2.3.1.1 15-1.2.2.2.1.1 15-1.2.2.3.1.1 16-1.2.2 17-1.2.2.3.2.1 20-1.2.2.2.1.1 20-1.2.2.3.1.1 22-1.2.2.2.1.1 22-1.2.2.3.1.1 24-1.2.1.1.1 26-1.2.1.1.2 27-1.2.1.2.1 31-1.2.1.2 33-1.2.1.2.1.1.1 35-1.2.1.2.1.1.1 36-1.2.1.2.1 37-1.2.1.2.1.2 39-1.2.1.2.1.2.1.1 39-1.2.1.2.1.2.1.1.4 39-1.2.1.2.1.2.1.1.4.r 40-1.2.1.2.1.2.1.1.1.1 43-1.2.1.2.1.2.1.1.1.1 46-1.2.1.2.1.2.1.1.3.1 51-1.2.1.2.1.2.1.1.2.1.1.1 55-1.2.1.2.1.2.1.2 56-1.2.1.2.1.2.1.2.1 58-1.2.1.2.1.2.1.3.1.1 59-1.2.1.2.1.2.1 59-1.2.1.2.1.2.1.3 59-1.2.1.2.1.2.1.3.r 61-1.2.1 61-1.2.1.2.1.2.1.3.1 61-1.2.1.2.1.2.1.3.2 62-1.2.1.2.1.2.1.3.1 64-1.2.1.2.1.2.2 64-1.2.1.2.1.2.2.r
(e / establish-01~e.4
:ARG1 (c / cell-line~e.1,2
:ARG1-of (s / stable-03~e.0))
:manner (t / transfect-01
:ARG1 (c2 / cell~e.61
:mod (b / between :op1 7~e.24 :op2 4~e.26)
:ARG1-of (d3 / derive-01~e.31
:ARG2 (c3 / cell-line~e.27,36
:name (n3 / name :op1 "NIH/3T3"~e.33,35)
:ARG0-of (h / harbor-01~e.37
:ARG1 (a / and~e.59
:op1 (g / gene~e.39
:name (n5 / name :op1 "Ha-ras"~e.40,43)
:ARG1-of (d4 / describe-01
:ARG0 (p / publication-91
:ARG1-of (c4 / cite-01 :ARG2 23~e.51)))
:ARG2-of (m / mutate-01 :value "V12"~e.46)
:ARG2-of~e.39 (i / induce-01~e.39
:ARG1-of (p2 / possible-01))
:ARG0-of (c7 / cause-01
:ARG1 (d / disease :wiki "Cancer"
:name (n7 / name :op1 "cancer"))))
:op2 (d5 / designate-01~e.55
:ARG1 (v2 / vector~e.56))
:op3~e.59 (a2 / and~e.59
:op1 (c5 / cell-line~e.61,62
:mod (w3 / wild-type~e.58))
:op2 (c6 / cell-line~e.61
:mod (k3 / knock-down-02))))
:manner~e.64 (r / respective~e.64)))))
:ARG2 (o / or~e.16
:op1 (n4 / nucleic-acid :wiki "DNA"
:name (n6 / name :op1 "DNA"~e.8)
:mod (v / vector~e.7))
:op2 (e2 / enzyme
:name (n / name :op1 "Aurora-A"~e.13,15,20,22)
:mod (w / wild-type~e.10,12))
:op3 (e3 / enzyme
:name (n2 / name :op1 "Aurora-A"~e.13,15,20,22)
:ARG1-of (d2 / deactivate-01
:ARG0 (k / kinase~e.17))))))
# ::id pmid_2000_3375.119 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The expression levels of Ha @- @ ras @ V12 @ in Vector , WT and KD cells in the presence of IPTG were much higher compared to the cells without IPTG ( Figure 2A ) .
# ::alignments 1-1.1.1 1-1.3.1 2-1.1 2-1.3 3-1.1.1.1.r 4-1.1.1.1.1.1 7-1.1.1.1.1.1 10-1.1.1.1.2.1 12-1.1.1.2.r 13-1.1.1.2.1.1 15-1.1.1.2.2.1 16-1.1.1.2 18-1.1.1.2.1 18-1.1.1.2.2 18-1.1.1.2.3 18-1.3.1.1 22-1.1.2.r 23-1.1.2.1.1 25-1.2.1 26-1 26-1.2 26-1.2.r 27-1.3.r 30-1.1.1.2.2 32-1.1.2.1.1 34-1.4.1 36-1.4.1.1
(h / high-02~e.26
:ARG1 (l / level~e.2
:degree-of (e / express-03~e.1
:ARG2~e.3 (g / gene
:name (n / name :op1 "Ha-ras"~e.4,7)
:ARG2-of (m3 / mutate-01 :value "V12"~e.10))
:ARG3~e.12 (a2 / and~e.16
:op1 (c / cell~e.18
:mod (v / vector~e.13))
:op2 (c2 / cell~e.18,30
:mod (w / wild-type~e.15))
:op3 (c3 / cell~e.18
:mod (k / knock-down-02))))
:condition~e.22 (s2 / small-molecule
:name (n2 / name :op1 "IPTG"~e.23,32)))
:degree~e.26 (m / more~e.26
:degree (m2 / much~e.25))
:compared-to~e.27 (l2 / level~e.2
:degree-of (e3 / express-03~e.1
:ARG3 (c4 / cell~e.18
:ARG0-of (l3 / lack-01
:ARG1 s2))))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.34 :mod "2A"~e.36)))
# ::id pmid_2000_3375.120 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Aurora @-@ A can physically interact with the tail of Histone H3 ( H3 ) and efficiently phosphorylates H3 at serine10 [ @ 45 @ - @ 48 @ ] .
# ::alignments 0-1.1.1.1.1.1 2-1.1.1.1.1.1 3-1.1 4-1.1.1.3 5-1.1.1 6-1.1.1.2.r 8-1.1.1.2 9-1.1.1.2.1.r 10-1.1.1.2.1.1.1 11-1.1.1.2.1.1.2 15-1 16-1.2.3 17-1.2 23-1.3.1.1.1.1 27-1.3.1.1.1.2
(a / and~e.15
:op1 (p / possible-01~e.3
:ARG1 (i / interact-01~e.5
:ARG0 (e / enzyme
:name (n / name :op1 "Aurora-A"~e.0,2))
:ARG1~e.6 (t / tail~e.8
:part-of~e.9 (p2 / protein
:name (n2 / name :op1 "Histone"~e.10 :op2 "H3"~e.11)))
:ARG2 (p5 / physical~e.4)))
:op2 (p3 / phosphorylate-01~e.17
:ARG1 (a3 / amino-acid :mod 10
:name (n3 / name :op1 "serine")
:part-of p2)
:ARG2 e
:ARG2-of (e2 / efficient-01~e.16))
:ARG1-of (d / describe-01
:ARG0 (p4 / publication-91
:ARG1-of (c / cite-01
:ARG2 (v / value-interval :op1 45~e.23 :op2 48~e.27)))))
# ::id pmid_2000_3375.121 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In addition , activation of ERK pathway in Ha @- @ ras @ transformed mouse fibroblasts increases the level of p @-@ H3S10 .
# ::alignments 0-1 1-1 3-1.1.1 4-1.1.1.1.r 5-1.1.1.1.1.1 6-1.1.1.1 7-1.1.1.2.r 8-1.1.1.2.2.1.1.1 11-1.1.1.2.2.1.1.1 13-1.1.1.2.2 14-1.1.1.2.1 15-1.1.1.2 16-1.1 18-1.1.2 19-1.1.2.1.r 20-1.1.2.1.4
(a / and~e.0,1
:op2 (i / increase-01~e.16
:ARG0 (a2 / activate-01~e.3
:ARG1~e.4 (p / pathway~e.6
:name (n / name :op1 "ERK"~e.5))
:location~e.7 (f / fibroblast~e.15
:source (m / mouse~e.14)
:ARG1-of (t / transform-01~e.13
:ARG0 (g / gene
:name (n2 / name :op1 "Ha-ras"~e.8,11)))))
:ARG1 (l / level~e.18
:quant-of~e.19 (a4 / amino-acid :mod 10
:name (n5 / name :op1 "serine")
:part-of (p2 / protein
:name (n4 / name :op1 "H3"))
:ARG3-of (p3 / phosphorylate-01~e.20)))))
# ::id pmid_2000_3375.122 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Consistently , our data showed the level of phosphorylated H3S10 ( p @-@ H3S10 detected by anti @-@ p @-@ H3S10 antibody ) in WT cells ( Figure 2A , lane 2 , 1.8 fold ) was higher than in Vector cells ( Figure 2A , lane 1 , 1.0 fold ) and KD cells ( Figure 2A , lane 3 , 0.9 fold ) in the absent of IPTG where Ras was not overexpressed .
# ::alignments 0-1.3 2-1.1.1 2-1.1.1.r 3-1.1 4-1 6-1.2.1 7-1.2.1.1.r 8-1.2.1.1.3 11-1.2.1.1.3 14-1.2.1.1.4 15-1.2.1.1.4.1.r 16-1.2.1.1.4.1.1 18-1.2.1.1.3 21-1.2.1.1.4.1 24-1.2.1.3.1 25-1.2.1.3 27-1.2.1.2.1.2 29-1.2.1.2.1.2.1 32-1.2.1.2.1 33-1.2.1.2.1.1 35-1.2.1.2.2.1 36-1.2.1.2.2 39-1.2 39-1.2.2 39-1.2.2.r 40-1.2.3.r 42-1.2.3.1.1 43-1.2.3.1 45-1.2.3.1.2.1.2 46-1.2.3.1.2.1.2 47-1.2.3.1.2.1.2 50-1.2.3.1.2.1 51-1.2.3.1.2.1.1 53-1.2.3.1.2.2.1 54-1.2.3.1.2.2 56-1.2.3 58-1.2.3.1 58-1.2.3.2 60-1.2.3.2.2.1.2 61-1.2.3.2.2.1.2 62-1.2.3.2.2.1.2 65-1.2.3.2.2.1 66-1.2.3.2.2.1.1 68-1.2.3.2.2.2.1 69-1.2.3.2.2.2 71-1.2.4.r 73-1.2.4.1 74-1.2.4.1.1.r 75-1.2.4.1.1.1.1 76-1.2.1.3.r 77-1.2.4.2.2.1.1 79-1.2.4.2.1 79-1.2.4.2.1.r 80-1.2.4.2
(s / show-01~e.4
:ARG0 (d / data~e.3
:poss~e.2 (w / we~e.2))
:ARG1 (h / high-02~e.39
:ARG1 (l / level~e.6
:quant-of~e.7 (a5 / amino-acid :mod 10
:name (n / name :op1 "serine")
:ARG3-of (p2 / phosphorylate-01~e.8,11,18)
:ARG1-of (d2 / detect-01~e.14
:ARG0~e.15 (a / antibody~e.21
:ARG0-of (c5 / counter-01~e.16
:ARG1 a5)))
:part-of (p / protein
:name (n5 / name :op1 "H3")))
:ARG1-of (d3 / describe-01
:part-of (l2 / lane~e.32 :mod 2~e.33
:part-of (f2 / figure~e.27 :mod "2A"~e.29))
:quant (p4 / product-of~e.36 :op1 1.8~e.35))
:location~e.76 (c / cell~e.25
:mod (w2 / wild-type~e.24)))
:degree~e.39 (m / more~e.39)
:compared-to~e.40 (a3 / and~e.56
:op1 (c2 / cell~e.43,58
:mod (v / vector~e.42)
:ARG1-of (d4 / describe-01
:part-of (l3 / lane~e.50 :mod 1~e.51
:part-of f2~e.45,46,47)
:quant (p5 / product-of~e.54 :op1 1.0~e.53)))
:op2 (c3 / cell~e.58
:mod (k / knock-down-02)
:ARG1-of (d5 / describe-01
:part-of (l4 / lane~e.65 :mod 3~e.66
:part-of f2~e.60,61,62)
:quant (p6 / product-of~e.69 :op1 0.9~e.68))))
:condition~e.71 (a6 / and
:op1 (a7 / absent-01~e.73
:ARG1~e.74 (s2 / small-molecule
:name (n3 / name :op1 "IPTG"~e.75)))
:op2 (o / overexpress-01~e.80 :polarity~e.79 -~e.79
:ARG1 (e2 / enzyme
:name (n4 / name :op1 "Ras"~e.77)))))
:manner (c4 / consistent-02~e.0))
# ::id pmid_2000_3375.123 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Our data showed that the Aurora @-@ A overexpressed in WT cells is functional .
# ::alignments 0-1.1.1 0-1.1.1.r 1-1.1 2-1 3-1.2.r 5-1.2.1.1.1 7-1.2.1.1.1 8-1.2.1.2 9-1.2.1.2.1.r 10-1.2.1.2.1.1 11-1.2.1.2.1 13-1.2
(s / show-01~e.2
:ARG0 (d / data~e.1
:poss~e.0 (w / we~e.0))
:ARG1~e.3 (f / function-01~e.13
:ARG0 (e / enzyme
:name (n / name :op1 "Aurora-A"~e.5,7)
:ARG1-of (o / overexpress-01~e.8
:location~e.9 (c / cell~e.11
:mod (w2 / wild-type~e.10))))))
# ::id pmid_2000_3375.124 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In the presence of IPTG , where Ras @ V12 @ protein was overexpressed , the level of phosphorylated H3S10 was increased both in Vector ( Figure 2A , lane 4 , 2.8 fold ) , WT ( Figure 2A , lane 5 , 3.8 fold ) and KD ( Figure 2A , lane 6 , 2.8 fold ) cells .
# ::alignments 3-1.2.1.1.1.2 4-1.3.1.1.1 6-1.2.r 7-1.3.2.1.1.1 9-1.3.2.1.2.1 11-1.1.1.4 13-1.3.2 16-1.1 18-1.1.1.3 21-1 24-1.2.1.1 26-1.2.1.1.1.1.2 28-1.2.1.1.1.1.2.1 31-1.2.1.1.1.1 32-1.2.1.1.1.1.1 34-1.2.1.1.1.2.1 34-1.2.3.1.1.2.1 35-1.2.1.1.1.2 35-1.2.3.1.1.2 38-1.2.2.1 40-1.2.2.1.1.1.2 41-1.2.2.1.1.1.2 42-1.2.2.1.1.1.2 45-1.2.2.1.1.1 46-1.2.2.1.1.1.1 48-1.2.2.1.1.2.1 49-1.2.2.1.1.2 51-1.2 54-1.2.3.1.1.1.2 55-1.2.3.1.1.1.2 56-1.2.3.1.1.1.2 59-1.2.3.1.1.1 60-1.2.3.1.1.1.1 62-1.2.3.1.1.2.1 63-1.2.3.1.1.2 65-1.2.1 65-1.2.2 65-1.2.3
(i / increase-01~e.21
:ARG1 (l / level~e.16
:quant-of (a3 / amino-acid :mod 10
:name (n / name :op1 "serine")
:ARG3-of (p2 / phosphorylate-01~e.18)
:part-of (p / protein~e.11
:name (n4 / name :op1 "H3"))))
:location~e.6 (a4 / and~e.51
:op1 (c / cell~e.65
:mod (v / vector~e.24
:ARG1-of (d / describe-01
:ARG0 (l2 / lane~e.31 :mod 4~e.32
:part-of (f2 / figure~e.26 :mod "2A"~e.28))
:quant (p4 / product-of~e.3,35 :op1 2.8~e.34))))
:op2 (c2 / cell~e.65
:mod (w / wild-type~e.38
:ARG1-of (d2 / describe-01
:ARG0 (l3 / lane~e.45 :mod 5~e.46
:part-of f2~e.40,41,42)
:quant (p5 / product-of~e.49 :op1 3.8~e.48))))
:op3 (c3 / cell~e.65
:mod (k / knock-down-02
:ARG1-of (d3 / describe-01
:ARG0 (l4 / lane~e.59 :mod 6~e.60
:part-of f2~e.54,55,56)
:quant (p6 / product-of~e.35,63 :op1 2.8~e.34,62)))))
:condition (a5 / and
:op1 (s / small-molecule
:name (n2 / name :op1 "IPTG"~e.4))
:op2 (o / overexpress-01~e.13
:ARG1 (e / enzyme
:name (n3 / name :op1 "Ras"~e.7)
:ARG2-of (m / mutate-01 :value "V12"~e.9)))))
# ::id pmid_2000_3375.125 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Biological activity analysis showed that WT cells over @-@ expressing wild @-@ type Aurora @-@ A became rounded and formed aggregates in the presence of IPTG compared to the Vector cells and KD cells ( Figure 2B ) .
# ::alignments 0-1.1.1.1 1-1.1.1 2-1.1 3-1 4-1.2.r 5-1.2.1.1.1 5-1.2.1.1.2.1.2 6-1.2.1.1 10-1.2.1.1.1 10-1.2.1.1.2.1.2 12-1.2.1.1.1 12-1.2.1.1.2.1.2 13-1.2.1.1.2.1.1.1 15-1.2.1.1.2.1.1.1 17-1.2.1 18-1.2 19-1.2.2 20-1.2.2.2 25-1.2.3.1.1 26-1.2.1.1.3.r 29-1.2.1.1.3.1.1 30-1.2.1.1.3.1 30-1.2.1.1.3.2 33-1.2.1.1.3.1 35-1.3.1 37-1.3.1.1
(s / show-01~e.3
:ARG0 (a / analyze-01~e.2
:ARG1 (a2 / activity-06~e.1
:mod (b / biology~e.0)))
:ARG1~e.4 (a3 / and~e.18
:op1 (r / round-04~e.17
:ARG1 (c / cell~e.6
:mod (w / wild-type~e.5,10,12)
:ARG0-of (o / overexpress-01
:ARG1 (e / enzyme
:name (n / name :op1 "Aurora-A"~e.13,15)
:mod (w2 / wild-type~e.5,10,12)))
:compared-to~e.26 (a5 / and
:op1 (c2 / cell~e.30,33
:mod (v / vector~e.29))
:op2 (c3 / cell~e.30
:mod (k / knock-down-02)))))
:op2 (f / form-01~e.19
:ARG0 c
:ARG1 (a4 / aggregate-01~e.20))
:condition (s2 / small-molecule
:name (n2 / name :op1 "IPTG"~e.25)))
:ARG1-of (d / describe-01
:ARG0 (f2 / figure~e.35 :mod "2B"~e.37)))
# ::id pmid_2000_3375.126 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Transforming analysis showed that WT cells form more foci compared to Vector and KD cells ( Figure 2C ) .
# ::alignments 0-1.1.1 1-1.1 2-1 3-1.2.r 4-1.2.1.1 5-1.2.1 6-1.2 7-1.2.2.1 8-1.2.2 9-1.2.3.r 11-1.2.3.1.1 12-1.2.3 14-1.2.3.1 14-1.2.3.2 16-1.3.1 18-1.3.1.1
(s / show-01~e.2
:ARG0 (a / analyze-01~e.1
:mod (t / transform-01~e.0))
:ARG1~e.3 (f / form-01~e.6
:ARG0 (c / cell~e.5
:mod (w / wild-type~e.4))
:ARG1 (f2 / focus~e.8
:mod (m / more~e.7))
:compared-to~e.9 (a3 / and~e.12
:op1 (c2 / cell~e.14
:mod (v / vector~e.11))
:op2 (c3 / cell~e.14
:mod (k / knock-down-02))))
:ARG1-of (d / describe-01
:ARG0 (f3 / figure~e.16 :mod "2C"~e.18)))
# ::id pmid_2000_3375.127 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Despite the fact that focus numbers were also increased in the other two cell lines , a further increase of focus number in WT cells was observed after IPTG induction ( Figure 2C ) .
# ::alignments 0-1.4.r 4-1.4.1 5-1.4.1 7-1.4.2 8-1.4 9-1.4.3.r 11-1.4.3.2 12-1.4.3.1 13-1.4.3 14-1.4.3 17-1.1.2 18-1.1 19-1.1.1.r 20-1.1.1.1 21-1.1.1 22-1.1.3.r 23-1.1.3.1 24-1.1.3 26-1 27-1.2 28-1.2.1.1.1.1 29-1.2.1 31-1.3.1 33-1.3.1.1
(o / observe-01~e.26
:ARG1 (i / increase-01~e.18
:ARG1~e.19 (n / number~e.21
:quant-of (f / focus~e.20))
:degree (f2 / further~e.17)
:location~e.22 (c / cell~e.24
:mod (w / wild-type~e.23)))
:time (a / after~e.27
:op1 (i2 / induce-01~e.29
:ARG2 (s / small-molecule
:name (n2 / name :op1 "IPTG"~e.28))))
:ARG1-of (d / describe-01
:ARG0 (f5 / figure~e.31 :mod "2C"~e.33))
:concession~e.0 (i3 / increase-01~e.8
:ARG1 n~e.4,5
:mod (a2 / also~e.7)
:location~e.9 (c2 / cell-line~e.13,14 :quant 2~e.12
:mod (o2 / other~e.11))))
# ::id pmid_2000_3375.128 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Taken together , both Aurora @-@ A and mutant Ras @ V12 @ overexpression can induce focus formation .
# ::alignments 0-1.2 1-1.2.2 4-1.1.1.1.1.1.1.1 6-1.1.1.1.1.1.1.1 7-1.1.1.1 8-1.1.1.1.2.1 8-1.1.1.1.2.1.2 8-1.1.1.1.2.1.2.r 9-1.1.1.1.2.1.1.1 11-1.1.1.1.2.1.2.1 13-1.1.1.1.1 13-1.1.1.1.2 14-1.1 15-1.1.1 16-1.1.1.2.1 17-1.1.1.2
(h / have-condition-91
:ARG1 (p / possible-01~e.14
:ARG1 (i / induce-01~e.15
:ARG0 (a / and~e.7
:op1 (o / overexpress-01~e.13
:ARG1 (e / enzyme
:name (n / name :op1 "Aurora-A"~e.4,6)))
:op2 (o2 / overexpress-01~e.13
:ARG1 (e2 / enzyme~e.8
:name (n2 / name :op1 "Ras"~e.9)
:ARG2-of~e.8 (m / mutate-01~e.8 :value "V12"~e.11))))
:ARG2 (f / form-01~e.17
:ARG1 (f2 / focus~e.16))))
:ARG2 (t / take-01~e.0
:ARG1 a
:mod (t2 / together~e.1)))
# ::id pmid_2000_3375.129 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Further induction of focus formation was detected when these two genes were overexpressed simultaneously .
# ::alignments 0-1.1.2 1-1.1 2-1.1.1.r 3-1.1.1.1 4-1.1.1 6-1 8-1.2.1.2 9-1.2.1.1 10-1.2.1 12-1.2 13-1.2.2
(d / detect-01~e.6
:ARG1 (i / induce-01~e.1
:ARG2~e.2 (f2 / form-01~e.4
:ARG1 (f3 / focus~e.3))
:degree (f / further~e.0))
:condition (o / overexpress-01~e.12
:ARG1 (g / gene~e.10 :quant 2~e.9
:mod (t / this~e.8))
:mod (s / simultaneous~e.13)))
# ::id pmid_2000_3375.130 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Cell proliferation analysis showed that WT cells grew slower than Vector and KD cells in the absence of IPTG .
# ::alignments 0-1.1.1.1 1-1.1.1 2-1.1 3-1 4-1.2.r 5-1.2.1.1 6-1.2.1 7-1.2 8-1.2.2 8-1.2.2.1 8-1.2.2.1.r 9-1.2.2.2.r 10-1.2.2.2.1.1 11-1.2.2.2 13-1.2.2.2.1 13-1.2.2.2.2 14-1.2.3.r 16-1.2.3 17-1.2.3.1.r 18-1.2.3.1.1.1
(s / show-01~e.3
:ARG0 (a / analyze-01~e.2
:ARG1 (p / proliferate-01~e.1
:ARG0 (c / cell~e.0)))
:ARG1~e.4 (g / grow-01~e.7
:ARG1 (c2 / cell~e.6
:mod (w / wild-type~e.5))
:ARG2 (s2 / slow-05~e.8
:degree~e.8 (m / more~e.8)
:compared-to~e.9 (a2 / and~e.11
:op1 (c3 / cell~e.13
:mod (v / vector~e.10))
:op2 (c4 / cell~e.13
:mod (k / knock-down-02))))
:condition~e.14 (a3 / absent-01~e.16
:ARG1~e.17 (s3 / small-molecule
:name (n / name :op1 "IPTG"~e.18)))))
# ::id pmid_2000_3375.131 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Growth rate of Vector , WT and KD cells were decreased when mutant Ras was overexpressed ( Fig . 2D ) .
# ::alignments 0-1.1.1.1 0-1.1.2.1 0-1.1.3.1 1-1.1.1 1-1.1.2 1-1.1.3 3-1.1.1.1.1.1 5-1.1.2.1.1.1 6-1.1 8-1.1.1.1.1 8-1.1.2.1.1 8-1.1.3.1.1 10-1 11-1.2.r 12-1.2.1 12-1.2.1.2 12-1.2.1.2.r 13-1.2.1.1.1 15-1.2 17-1.3.1 20-1.3.1.1
(d / decrease-01~e.10
:ARG1 (a / and~e.6
:op1 (r / rate~e.1
:degree-of (g / grow-01~e.0
:ARG1 (c / cell~e.8
:mod (v / vector~e.3))))
:op2 (r2 / rate~e.1
:degree-of (g2 / grow-01~e.0
:ARG1 (c2 / cell~e.8
:mod (w / wild-type~e.5))))
:op3 (r3 / rate~e.1
:degree-of (g3 / grow-01~e.0
:ARG1 (c3 / cell~e.8
:mod (k / knock-down-02)))))
:time~e.11 (o / overexpress-01~e.15
:ARG1 (e / enzyme~e.12
:name (n / name :op1 "Ras"~e.13)
:ARG2-of~e.12 (m / mutate-01~e.12)))
:ARG1-of (d2 / describe-01
:ARG0 (f / figure~e.17 :mod "2D"~e.20)))
# ::id pmid_2000_3375.132 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The increase of cell aggregation of WT cells in the presence of IPTG was independent of cell growth rate .
# ::alignments 1-1.2 2-1.2.1.r 3-1.2.1.1 3-1.2.1.2 4-1.2.1 6-1.2.1.1.1 7-1.2.1.1 8-1.2.2.r 10-1.2.2 11-1.2.2.1.r 12-1.2.2.1.1.1 14-1 14-1.1 14-1.1.r 15-1.3.r 16-1.3.1.1 17-1.3.1 18-1.3
(d / depend-01~e.14 :polarity~e.14 -~e.14
:ARG0 (i / increase-01~e.1
:ARG1~e.2 (a / aggregate-01~e.4
:ARG1 (c / cell~e.3,7
:mod (w / wild-type~e.6))
:mod (c2 / cell~e.3))
:condition~e.8 (p / present-02~e.10
:ARG1~e.11 (s / small-molecule
:name (n / name :op1 "IPTG"~e.12))))
:ARG1~e.15 (r / rate~e.18
:degree-of (g / grow-01~e.17
:ARG1 c~e.16)))
# ::id pmid_2000_3375.133 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Aurora @-@ A overexpression increases phosphorylation status of MEK @/@ ERK and AKT as well as the activity of RalA in the Ras @ V12 @ transformants
# ::alignments 1-1.1.1.1.1 3-1.1.1.1.1 4-1.1 5-1 6-1.2.1.1 7-1.2.1 8-1.2.1.2.r 9-1.2.1.2.1.1.1 11-1.2.1.2.1.1.1 12-1.2.1.2 13-1.2.1.2.2.1.1 14-1.2 15-1.2 16-1.2 16-1.2.r 18-1.2.2 19-1.2.2.1.r 20-1.2.2.1.1.1 21-1.2.2.2.r 23-1.2.2.2.1.1 25-1.2.2.2.2.1 27-1.2.2.2 27-1.2.2.2.2 27-1.2.2.2.2.r
(i / increase-01~e.5
:ARG0 (o / overexpress-01~e.4
:ARG1 (e2 / enzyme
:name (n / name :op1 "Aurora-A"~e.1,3)))
:ARG1~e.16 (a2 / and~e.14,15,16
:op1 (s / status~e.7
:mod (p / phosphorylate-01~e.6)
:poss~e.8 (a / and~e.12
:op1 (p2 / pathway
:name (n2 / name :op1 "MEK/ERK"~e.9,11))
:op2 (p4 / pathway
:name (n3 / name :op1 "AKT"~e.13))))
:op2 (a3 / activity-06~e.18
:ARG0~e.19 (p3 / protein
:name (n4 / name :op1 "RalA"~e.20))
:location~e.21 (e3 / enzyme~e.27
:name (n5 / name :op1 "Ras"~e.23)
:ARG2-of~e.27 (t / transform-01~e.27 :value "V12"~e.25)))))
# ::id pmid_2000_3375.134 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To clarify the effects of Aurora @-@ A on the signaling pathways related to Ras overexpression , three downstream signaling pathways of Ras , Raf/MEK , PI3K @/@ AKT and RalGDS @/@ Ral A were investigated .
# ::alignments 1-1.2 3-1.2.1 4-1.2.1.1.r 5-1.2.1.1.1.1 7-1.2.1.1.1.1 8-1.2.1.2.r 10-1.2.1.2.1 11-1.2.1.2 12-1.2.1.2.2 13-1.2.1.2.2.1.r 14-1.2.1.2.2.1.1 15-1.2.1.2.2.1 17-1.1.1 18-1.1.2 19-1.1.3 20-1.1 21-1.1.3.1.r 22-1.1.3.1.1.1 24-1.1.4.1.1.1.1 26-1.1.4.1.2.1.1 28-1.1.4.1.2.1.1 29-1.1.4.1 30-1.1.4.1.3.1.1 33-1.2.1.1.1.1 35-1
(i / investigate-01~e.35
:ARG1 (p / pathway~e.20 :quant 3~e.17
:location (d / downstream~e.18)
:ARG0-of (s / signal-07~e.19
:ARG1~e.21 (e / enzyme
:name (n / name :op1 "Ras"~e.22)))
:ARG1-of (m / mean-01
:ARG2 (a / and~e.29
:op1 (p2 / pathway
:name (n2 / name :op1 "Raf/MEK"~e.24))
:op2 (p3 / pathway
:name (n3 / name :op1 "PI3K/AKT"~e.26,28))
:op3 (p4 / pathway
:name (n4 / name :op1 "RalGDS/RalA"~e.30)))))
:ARG2 (c / clarify-10~e.1
:ARG1 (a2 / affect-01~e.3
:ARG0~e.4 (e2 / enzyme
:name (n5 / name :op1 "Aurora-A"~e.5,7,33))
:ARG1~e.8 (p6 / pathway~e.11
:ARG0-of s~e.10
:ARG1-of (r / relate-01~e.12
:ARG2~e.13 (o / overexpress-01~e.15
:ARG2 e~e.14))))))
# ::id pmid_2000_3375.135 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The phosphorylation of MEK ( p @-@ MEK ) was higher in WT cells ( Figure 3A , lane 2 , 1.7 fold ) than that in Vector ( Figure 3A , lane 1 , 1.0 fold ) and KD cells ( Figure 3A , lane 3 , 0.8 fold ) .
# ::alignments 1-1.4 3-1.1.1.1.1 5-1.1 7-1.1.1.1.1 10-1 10-1.2 10-1.2.r 11-1.3.r 12-1.3.1 13-1.3 15-1.3.2.1.2 17-1.3.2.1.2.1 20-1.3.2.1 21-1.3.2.1.1 23-1.3.2.2.1 24-1.3.2.2 26-1.4.r 28-1.4.2.r 29-1.4.2.1.1 31-1.4.2.1.2.1.2 32-1.4.2.1.2.1.2 33-1.4.2.1.2.1.2 36-1.4.2.1.2.1 37-1.4.2.1.2.1.1 39-1.4.2.1.2.2.1 40-1.4.2.1.2.2 42-1.4.2 44-1.4.2.1 44-1.4.2.2 46-1.4.2.2.2.1.2 47-1.4.2.2.2.1.2 48-1.4.2.2.2.1.2 51-1.4.2.2.2.1 52-1.4.2.2.2.1.1 54-1.4.2.2.2.2.1 55-1.4.2.2.2.2
(h / high-02~e.10
:ARG1 (p / phosphorylate-01~e.5
:ARG1 (e / enzyme
:name (n / name :op1 "MEK"~e.3,7)))
:degree~e.10 (m / more~e.10)
:location~e.11 (c / cell~e.13
:mod (w / wild-type~e.12)
:ARG1-of (d / describe-01
:ARG0 (l2 / lane~e.20 :mod 2~e.21
:part-of (f / figure~e.15 :mod "3A"~e.17))
:ARG2 (p3 / product-of~e.24 :op1 1.7~e.23)))
:compared-to~e.26 (p2 / phosphorylate-01~e.1
:ARG1 e
:location~e.28 (a / and~e.42
:op1 (c2 / cell~e.44
:mod (v / vector~e.29)
:ARG1-of (d2 / describe-01
:ARG0 (l3 / lane~e.36 :mod 1~e.37
:part-of f~e.31,32,33)
:ARG2 (p4 / product-of~e.40 :op1 1.0~e.39)))
:op2 (c3 / cell~e.44
:mod (k / knock-down-02)
:ARG1-of (d3 / describe-01
:ARG0 (l4 / lane~e.51 :mod 3~e.52
:part-of f~e.46,47,48)
:ARG2 (p5 / product-of~e.55 :op1 0.8~e.54))))))
# ::id pmid_2000_3375.136 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok P @-@ MEK levels in each cell line were further increased after IPTG induction ( Ras @ V12 @ is over @-@ expressed ) ( Figure 3A , lane 4 , 5 , and 6 ) .
# ::alignments 0-1.1.2.2 2-1.1.2.1.1 3-1.1 4-1.1.1.r 5-1.1.1.1 6-1.1.1 7-1.1.1 9-1.2 10-1 11-1.3 12-1.3.1.1.1.1 13-1.3.1 15-1.4.1.1.1.1 17-1.4.1.1.2.1 25-1.5.1.4 27-1.5.1.4.1 30-1.5.1.1 30-1.5.1.2 30-1.5.1.3 31-1.5.1.1.1 33-1.5.1.2.1 35-1.5.1 36-1.5.1.3.1
(i / increase-01~e.10
:ARG1 (l / level~e.3
:location~e.4 (c / cell-line~e.6,7
:mod (e2 / each~e.5))
:quant-of (e / enzyme
:name (n / name :op1 "MEK"~e.2)
:ARG3-of (p / phosphorylate-01~e.0)))
:degree (f / further~e.9)
:time (a / after~e.11
:op1 (i2 / induce-01~e.13
:ARG2 (s / small-molecule
:name (n2 / name :op1 "IPTG"~e.12))))
:ARG1-of (m / mean-01
:ARG2 (o / overexpress-01
:ARG1 (e3 / enzyme
:name (n3 / name :op1 "Ras"~e.15)
:ARG2-of (m2 / mutate-01 :value "V12"~e.17))))
:ARG1-of (d / describe-01
:ARG0 (a2 / and~e.35
:op1 (l2 / lane~e.30 :mod 4~e.31)
:op2 (l3 / lane~e.30 :mod 5~e.33)
:op3 (l4 / lane~e.30 :mod 6~e.36)
:part-of (f2 / figure~e.25 :mod "3A"~e.27))))
# ::id pmid_2000_3375.137 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The same phenomenon was also been observed in p @-@ ERK1 @/@ 2 ( Figure 3A ) .
# ::alignments 1-1.1.1 2-1.1 4-1.2 6-1 7-1.3.r 8-1.3.3 10-1.3.1.1.1 11-1.3 14-1.4.1 16-1.4.1.1
(o / observe-01~e.6
:ARG1 (p / phenomenon~e.2
:ARG1-of (s / same-01~e.1))
:mod (a / also~e.4)
:condition~e.7 (s2 / slash~e.11
:op1 (e / enzyme
:name (n / name :op1 "ERK1"~e.10))
:op2 (e2 / enzyme
:name (n2 / name :op1 "ERK2"))
:ARG3-of (p2 / phosphorylate-01~e.8))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.14 :mod "3A"~e.16)))
# ::id pmid_2000_3375.138 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok These results indicated that Aurora @-@ A may further increase Ras induced MEK @/@ ERK phosphorylation .
# ::alignments 0-1.1.2 1-1.1 1-1.1.1 1-1.1.1.r 2-1 3-1.2.r 4-1.2.1.1.1.1 6-1.2.1.1.1.1 7-1.2 8-1.2.1.3 9-1.2.1 10-1.2.1.2.2.1.1.1 11-1.2.1.2.2 12-1.2.1.2.1.1.1 14-1.2.1.2.1.1.1 15-1.2.1.2
(i / indicate-01~e.2
:ARG0 (t / thing~e.1
:ARG2-of~e.1 (r / result-01~e.1)
:mod (t2 / this~e.0))
:ARG1~e.3 (p3 / possible-01~e.7
:ARG1 (i2 / increase-01~e.9
:ARG0 (e2 / enzyme
:name (n3 / name :op1 "Aurora-A"~e.4,6))
:ARG1 (p5 / phosphorylate-01~e.15
:ARG1 (p / pathway
:name (n2 / name :op1 "MEK/ERK"~e.12,14))
:ARG2-of (i3 / induce-01~e.11
:ARG0 (e / enzyme
:name (n / name :op1 "Ras"~e.10))))
:degree (f / further~e.8))))
# ::id pmid_2000_3375.139 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The effect of Aurora @-@ A on the PI3K @/@ AKT pathway was evaluated by detecting phosphorylation of AKT ( p @-@ AKT ) .
# ::alignments 1-1.1 2-1.1.1.r 3-1.1.1.1.1 5-1.1.1.1.1 6-1.1.2.r 8-1.1.2.1.1 10-1.1.2.1.1 11-1.1.2 13-1 14-1.2.r 15-1.2 16-1.2.1 18-1.2.1.1.1.1 20-1.2.1 22-1.2.1.1.1.1
(e / evaluate-01~e.13
:ARG1 (a / affect-01~e.1
:ARG0~e.2 (e3 / enzyme
:name (n2 / name :op1 "Aurora-A"~e.3,5))
:ARG1~e.6 (p4 / pathway~e.11
:name (n3 / name :op1 "PI3K/AKT"~e.8,10)))
:manner~e.14 (d / detect-01~e.15
:ARG1 (p2 / phosphorylate-01~e.16,20
:ARG1 (e2 / enzyme
:name (n / name :op1 "AKT"~e.18,22)))))
# ::id pmid_2000_3375.140 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The p @-@ AKT level was also higher in WT cells ( Figure 3A , lane 2 , 2.1 fold ) compared to Vector and KD cells ( Figure 3A , lane 1 , 1.0 fold and lane 3 , 1.1 fold , respectively ) .
# ::alignments 1-1.1.1.2 3-1.1.1.1.1 4-1.1 6-1.3 7-1 7-1.2 7-1.2.r 8-1.4.r 9-1.4.1 10-1.4 12-1.4.2.1.2 14-1.4.2.1.2.1 17-1.4.2.1 18-1.4.2.1.1 20-1.4.2.2.1 21-1.4.2.2 23-1.5.r 25-1.5.1.1 26-1.5 28-1.5.1 28-1.5.2 30-1.5.1.2.1.2 31-1.5.1.2.1.2 32-1.5.1.2.1.2 35-1.5.1.2.1 36-1.5.1.2.1.1 38-1.5.1.2.2.1 39-1.5.1.2.2 40-1.5 41-1.5.2.2.1 42-1.5.2.2.1.1 44-1.5.2.2.2.1 45-1.5.2.2.2
(h / high-02~e.7
:ARG1 (l / level~e.4
:quant-of (e / enzyme
:name (n / name :op1 "AKT"~e.3)
:ARG3-of (p / phosphorylate-01~e.1)))
:degree~e.7 (m / more~e.7)
:mod (a / also~e.6)
:location~e.8 (c / cell~e.10
:mod (w / wild-type~e.9)
:ARG1-of (d / describe-01
:ARG0 (l2 / lane~e.17 :mod 2~e.18
:part-of (f / figure~e.12 :mod "3A"~e.14))
:ARG2 (p2 / product-of~e.21 :op1 2.1~e.20)))
:compared-to~e.23 (a2 / and~e.26,40
:op1 (c2 / cell~e.28
:mod (v / vector~e.25)
:ARG1-of (d2 / describe-01
:ARG0 (l3 / lane~e.35 :mod 1~e.36
:part-of f~e.30,31,32)
:ARG2 (p3 / product-of~e.39 :op1 1.0~e.38)))
:op2 (c3 / cell~e.28
:mod (k / knock-down-02)
:ARG1-of (d3 / describe-01
:ARG0 (l4 / lane~e.41 :mod 3~e.42
:part-of f)
:ARG2 (p4 / product-of~e.45 :op1 1.1~e.44)))))
# ::id pmid_2000_3375.141 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Upon IPTG induction , Ras @ V12 @ overexpression increased the level of p @-@ AKT in Vector and KD cells ( Figure 3A , lane 4 , 1.8 fold and lane 6 , 2.1 fold , respectively ) .
# ::alignments 1-1.3.1.1.1 2-1.3 4-1.1.1.1.1 6-1.1.1.2.1 8-1.1 9-1 11-1.2 12-1.2.1.r 13-1.2.1.2 15-1.2.1.1.1 16-1.1.2.r 17-1.1.2.1.1 20-1.1.2.1 20-1.1.2.2 22-1.1.2.1.2.1.2 24-1.1.2.1.2.1.2.1 27-1.1.2.1.2.1 28-1.1.2.1.2.1.1 30-1.1.2.1.2.2.1 31-1.1.2.1.2.2 32-1.1.2 33-1.1.2.2.2.1 34-1.1.2.2.2.1.1 36-1.1.2.2.2.2.1 37-1.1.2.2.2.2
(i / increase-01~e.9
:ARG0 (o / overexpress-01~e.8
:ARG1 (e / enzyme
:name (n / name :op1 "Ras"~e.4)
:ARG2-of (m / mutate-01 :value "V12"~e.6))
:location~e.16 (a / and~e.32
:op1 (c / cell~e.20
:mod (v / vector~e.17)
:ARG1-of (d / describe-01
:ARG0 (l2 / lane~e.27 :mod 4~e.28
:part-of (f / figure~e.22 :mod "3A"~e.24))
:ARG2 (p2 / product-of~e.31 :op1 1.8~e.30)))
:op2 (c2 / cell~e.20
:mod (k / knock-down-02)
:ARG1-of (d2 / describe-01
:ARG0 (l3 / lane~e.33 :mod 6~e.34
:part-of f)
:ARG2 (p3 / product-of~e.37 :op1 2.1~e.36)))))
:ARG1 (l / level~e.11
:quant-of~e.12 (e2 / enzyme
:name (n2 / name :op1 "AKT"~e.15)
:ARG3-of (p / phosphorylate-01~e.13)))
:condition (i2 / induce-01~e.2
:ARG2 (s / small-molecule
:name (n3 / name :op1 "IPTG"~e.1))))
# ::id pmid_2000_3375.142 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Co @-@ expression of Ras @ V12 @ and wild @-@ type Aurora @-@ A in WT cells increases the level of p @-@ AKT ( Figure 3A , lane 5 , 3.5 fold ) as compared to Ras @ V12 @ overexpression alone ( Figure 3A , lane 4 , 1.8 fold ) .
# ::alignments 4-1.1.1.1.1.1 6-1.1.1.1.2.1 8-1.1.1 9-1.1.1.2.2 11-1.1.1.2.2 12-1.1.1.2.1.1 14-1.1.1.2.1.1 16-1.1.1.2.2 17-1.1.2 18-1 20-1.2 21-1.2.1.r 22-1.2.1.2 24-1.2.1.1.1 26-1.2.2.1.2 28-1.2.2.1.2.1 31-1.2.2.1 32-1.2.2.1.1 34-1.2.2.2.1 35-1.2.2.2 38-1.3.r 40-1.3.1 41-1.3.1 42-1.3.1 44-1.3 45-1.3.2 47-1.3.3.1.2 48-1.3.3.1.2 49-1.3.3.1.2 52-1.3.3.1 53-1.3.3.1.1 55-1.3.3.2.1 56-1.3.3.2
(i / increase-01~e.18
:ARG0 (c / coexpress-01
:ARG2 (a / and~e.8
:op1 (e / enzyme
:name (n / name :op1 "Ras"~e.4)
:ARG2-of (m / mutate-01 :value "V12"~e.6))
:op2 (e3 / enzyme
:name (n2 / name :op1 "Aurora-A"~e.12,14)
:mod (w / wild-type~e.9,11,16)))
:ARG3 (c2 / cell~e.17
:mod w))
:ARG1 (l / level~e.20
:quant-of~e.21 (e2 / enzyme
:name (n3 / name :op1 "AKT"~e.24)
:ARG3-of (p2 / phosphorylate-01~e.22))
:ARG1-of (d / describe-01
:ARG0 (l2 / lane~e.31 :mod 5~e.32
:part-of (f / figure~e.26 :mod "3A"~e.28))
:ARG2 (p3 / product-of~e.35 :op1 3.5~e.34)))
:compared-to~e.38 (o / overexpress-01~e.44
:ARG1 e~e.40,41,42
:mod (a2 / alone~e.45)
:ARG1-of (d2 / describe-01
:ARG0 (l3 / lane~e.52 :mod 4~e.53
:part-of f~e.47,48,49)
:ARG2 (p4 / product-of~e.56 :op1 1.8~e.55))))
# ::id pmid_2000_3375.143 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The RalGDS @/@ RalA signaling pathway was determined by detecting the activity of RalA using GST @-@ RalBD pull @-@ down assay .
# ::alignments 1-1.1.1.1 3-1.1.1.1 4-1.1.2 5-1.1 7-1 8-1.2.r 9-1.2 11-1.2.1 12-1.2.1.1.r 13-1.2.1.1.1.1 14-1.2.2 15-1.2.2.1.1.1.1.1 17-1.2.2.1.1.1.1.1 18-1.2.2.1.1 20-1.2.2.1.1 21-1.2.2.1
(d / determine-01~e.7
:ARG1 (p / pathway~e.5
:name (n / name :op1 "RalGDS/RalA"~e.1,3)
:ARG0-of (s / signal-07~e.4))
:manner~e.8 (d2 / detect-01~e.9
:ARG1 (a / activity-06~e.11
:ARG0~e.12 (p2 / protein
:name (n2 / name :op1 "RalA"~e.13)))
:manner (u / use-01~e.14
:ARG1 (a2 / assay-01~e.21
:manner (p3 / pull-down-08~e.18,20
:ARG3 (p4 / protein
:name (n3 / name :op1 "GST-RalBD"~e.15,17)))))))
# ::id pmid_2000_3375.144 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok As shown in Figure 3A , Aurora @-@ A overexpression alone activated RalA ( Figure 3A , lane 2 , 2.0 fold ) as compared to the parental Vector cells ( Figure 3A , lane 1 , 1.0 fold ) .
# ::alignments 1-1.5 2-1.5.1.r 3-1.5.1 4-1.5.1 5-1.5.1 8-1.1.1.1.1 10-1.1.1.1.1 11-1.1 12-1.1.2 13-1 14-1.2.1.1 16-1.3.1.2 18-1.3.1.2.1 21-1.3.1 22-1.3.1.1 24-1.3.2.1 25-1.3.2 28-1.4.r 31-1.4.1 32-1.4.2 33-1.4 35-1.4.3.1.2 36-1.4.3.1.2 37-1.4.3.1.2 40-1.4.3.1 41-1.4.3.1.1 43-1.4.3.2.1 44-1.4.3.2
(a / activate-01~e.13
:ARG0 (o / overexpress-01~e.11
:ARG1 (e / enzyme
:name (n / name :op1 "Aurora-A"~e.8,10))
:mod (a2 / alone~e.12))
:ARG1 (p2 / protein
:name (n2 / name :op1 "RalA"~e.14))
:ARG1-of (d / describe-01
:ARG0 (l / lane~e.21 :mod 2~e.22
:part-of (f / figure~e.16 :mod "3A"~e.18))
:ARG2 (p3 / product-of~e.25 :op1 2.0~e.24))
:compared-to~e.28 (c / cell~e.33
:mod (p4 / parental~e.31)
:mod (v / vector~e.32)
:ARG1-of (d2 / describe-01
:ARG0 (l2 / lane~e.40 :mod 1~e.41
:part-of f~e.35,36,37)
:ARG2 (p5 / product-of~e.44 :mod 1.0~e.43)))
:ARG1-of (s / show-01~e.1
:medium~e.2 f~e.3,4,5))
# ::id pmid_2000_3375.145 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok After IPTG induction , The RalA activity was increased by Ras @ V12 @ overexpression ( Figure 3A , lane 4 , 2.5 fold ) .
# ::alignments 0-1.3 1-1.3.1.1.1.1 2-1.3.1 5-1.2.1.1.1 6-1.2 8-1 9-1.1.r 10-1.1.1.1.1 12-1.1.1.2.1 14-1.1 16-1.4.1.2 18-1.4.1.2.1 21-1.4.1 22-1.4.1.1 24-1.4.2.1 25-1.4.2
(i / increase-01~e.8
:ARG0~e.9 (o / overexpress-01~e.14
:ARG1 (e / enzyme
:name (n3 / name :op1 "Ras"~e.10)
:ARG2-of (m / mutate-01 :value "V12"~e.12)))
:ARG1 (a / activity-06~e.6
:ARG0 (p / protein
:name (n2 / name :op1 "RalA"~e.5)))
:time (a2 / after~e.0
:op1 (i2 / induce-01~e.2
:ARG2 (s / small-molecule
:name (n / name :op1 "IPTG"~e.1))))
:ARG1-of (d / describe-01
:ARG0 (l / lane~e.21 :mod 4~e.22
:part-of (f / figure~e.16 :mod "3A"~e.18))
:ARG2 (p2 / product-of~e.25 :op1 2.5~e.24)))
# ::id pmid_2000_3375.146 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Co @-@ expression of Ras @ V12 @ and wild @-@ type Aurora @-@ A in WT cells increase the activity of RalA of Ras @ V12 @ ( Figure 3A , lane 5 , 3.7 fold ) .
# ::alignments 4-1.1.1.1.1.1 6-1.1.1.1.2.1 8-1.1.1 9-1.1.1.2.2 10-1.1.1.2.2 11-1.1.1.2.2 12-1.1.1.2.1.1 14-1.1.1.2.1.1 16-1.1.1.2.2 17-1.1.2 17-1.2.1.2 18-1 20-1.2 21-1.2.1.r 22-1.2.1.1.1 24-1.1.1.1.1.1 26-1.1.1.1.2.1 29-1.3.1.2 31-1.3.1.2.1 34-1.3.1 35-1.3.1.1 37-1.3.2.1 38-1.3.2
(i / increase-01~e.18
:ARG0 (c / coexpress-01
:ARG2 (a / and~e.8
:op1 (e / enzyme
:name (n2 / name :op1 "Ras"~e.4,24)
:ARG2-of (m / mutate-01 :value "V12"~e.6,26))
:op2 (e2 / enzyme
:name (n3 / name :op1 "Aurora-A"~e.12,14)
:mod w~e.9,10,11,16))
:ARG3 (c2 / cell~e.17
:mod (w / wild-type)))
:ARG1 (a2 / activity-06~e.20
:ARG0~e.21 (p2 / protein
:name (n / name :op1 "RalA"~e.22)
:location (c3 / cell~e.17
:mod e)))
:ARG1-of (d / describe-01
:ARG0 (l / lane~e.34 :mod 5~e.35
:part-of (f / figure~e.29 :mod "3A"~e.31))
:ARG2 (p3 / product-of~e.38 :op1 3.7~e.37)))
# ::id pmid_2000_3375.147 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Taken together , both Aurora @-@ A and Ras @ V12 @ increased the levels of p @-@ MEK , pERK1 @/@ 2 , and p @-@ AKT and the activation of RalA .
# ::alignments 0-1.2 1-1.2.2 4-1.1.1.1.1.1 6-1.1.1.1.1.1 7-1.1.1 8-1.1.1.2.1.1 10-1.1.1.2.2.1 12-1.1 14-1.1.2.1 14-1.1.2.2 14-1.1.2.3 15-1.1.2.1.1.r 16-1.1.2.1.1.2 18-1.1.2.1.1.1.1 21-1.1.2.2.1 24-1.1.2 25-1.1.2.1.1.2 27-1.1.2.3.1.1.1 28-1.1.2 30-1.1.2.4 31-1.1.2.4.1.r 32-1.1.2.4.1.1.1
(h / have-condition-91
:ARG1 (i / increase-01~e.12
:ARG0 (a / and~e.7
:op1 (e / enzyme
:name (n2 / name :op1 "Aurora-A"~e.4,6))
:op2 (e2 / enzyme
:name (n3 / name :op1 "Ras"~e.8)
:ARG2-of (m / mutate-01 :value "V12"~e.10)))
:ARG1 (a2 / and~e.24,28
:op1 (l / level~e.14
:quant-of~e.15 (e3 / enzyme
:name (n4 / name :op1 "MEK"~e.18)
:ARG3-of (p2 / phosphorylate-01~e.16,25)))
:op2 (l2 / level~e.14
:quant-of (s / slash~e.21
:op1 (e4 / enzyme
:name (n5 / name :op1 "ERK1"))
:op2 (e5 / enzyme
:name (n6 / name :op1 "ERK2"))
:ARG3-of p2))
:op3 (l3 / level~e.14
:quant-of (e6 / enzyme
:name (n7 / name :op1 "AKT"~e.27)
:ARG3-of p2))
:op4 (a3 / activate-01~e.30
:ARG1~e.31 (p3 / protein
:name (n / name :op1 "RalA"~e.32)))))
:ARG2 (t / take-01~e.0
:ARG1 a
:mod (t2 / together~e.1)))
# ::id pmid_2000_3375.148 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok This induction was further enhanced when Aurora @-@ A and Ras @ V12 @ were overexpressed simultaneously .
# ::alignments 0-1.1.1 1-1.1 3-1.2 4-1 5-1.3.r 6-1.3.1.1.1.1 8-1.3.1.1.1.1 9-1.3.1 10-1.3.1.2.1.1 12-1.3.1.2.2.1 15-1.3 16-1.3.2
(e2 / enhance-01~e.4
:ARG1 (i / induce-01~e.1
:mod (t / this~e.0))
:degree (f / further~e.3)
:time~e.5 (o / overexpress-01~e.15
:ARG1 (a / and~e.9
:op1 (e / enzyme
:name (n2 / name :op1 "Aurora-A"~e.6,8))
:op2 (e3 / enzyme
:name (n3 / name :op1 "Ras"~e.10)
:ARG2-of (m / mutate-01 :value "V12"~e.12)))
:mod (s / simultaneous~e.16)))
# ::id pmid_2000_3375.149 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To further confirm our results , Aurora @-@ A specific small interference RNA ( siRNA ) was used .
# ::alignments 1-1.2.2 2-1.2 3-1.2.1.2 3-1.2.1.2.r 4-1.2.1 4-1.2.1.1 4-1.2.1.1.r 6-1.1.2.1.1.1 8-1.1.2.1.1.1 9-1.1 9-1.1.2 9-1.1.2.r 10-1.1.1.1 11-1.1.1.2 12-1.1.1.3 17-1
(u / use-01~e.17
:ARG1 (n3 / nucleic-acid~e.9
:name (n / name :op1 "small"~e.10 :op2 "interference"~e.11 :op3 "RNA"~e.12)
:ARG1-of~e.9 (s / specific-02~e.9
:ARG2 (e / enzyme
:name (n2 / name :op1 "Aurora-A"~e.6,8))))
:ARG2 (c / confirm-01~e.2
:ARG1 (t / thing~e.4
:ARG2-of~e.4 (r2 / result-01~e.4)
:poss~e.3 (w / we~e.3))
:degree (f / further~e.1)))
# ::id pmid_2000_3375.150 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok As shown in Figure 3B , Aurora @-@ A specific siRNA decreased the expression level of Aurora @-@ A in WT cells .
# ::alignments 1-1.3 2-1.3.1.r 3-1.3.1 5-1.3.1.1 8-1.1.2.1.1.1 10-1.1.2.1.1.1 11-1.1 11-1.1.2 11-1.1.2.r 12-1.1.1.1 13-1 15-1.2.1 16-1.2 17-1.2.1.1.r 18-1.2.1.1 19-1.2.1.1 20-1.2.1.1 21-1.2.1.2.r 22-1.2.1.2.1 23-1.2.1.2
(d / decrease-01~e.13
:ARG0 (n3 / nucleic-acid~e.11
:name (n / name :op1 "siRNA"~e.12)
:ARG1-of~e.11 (s / specific-02~e.11
:ARG2 (e2 / enzyme
:name (n2 / name :op1 "Aurora-A"~e.8,10))))
:ARG1 (l / level~e.16
:degree-of (e / express-03~e.15
:ARG1~e.17 e2~e.18,19,20
:ARG3~e.21 (c / cell~e.23
:mod (w / wild-type~e.22))))
:ARG1-of (s2 / show-01~e.1
:medium~e.2 (f / figure~e.3 :mod "3B"~e.5)))
# ::id pmid_2000_3375.151 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Accordingly , levels of p @-@ MEK/p @-@ ERK , p @-@ AKT and activation of RalA were also decreased when Aurora @-@ A siRNA was introduced into WT cells upon IPTG induction .
# ::alignments 0-1.4 2-1.1.1 2-1.1.2 2-1.1.3 4-1.1.1.1.3 8-1.1.1.1.2.1.1 10-1.1.1.1.3 12-1.1.2.1.1.1 13-1.1 14-1.1.3.1 15-1.1.3.1.1.r 16-1.1.3.1.1.1.1 18-1.2 19-1 20-1.3.r 21-1.3.1.2.1.1 23-1.3.1.2.1.1 24-1.3.1.1.1 26-1.3 27-1.3.2.r 28-1.3.2.1 29-1.3.2 31-1.3.3.1.1.1 32-1.3.3
(d / decrease-01~e.19
:ARG1 (a / and~e.13
:op1 (l / level~e.2
:quant-of (s / slash
:op1 (e / enzyme
:name (n / name :op1 "MEK"))
:op2 (e2 / enzyme
:name (n2 / name :op1 "ERK"~e.8))
:ARG3-of (p / phosphorylate-01~e.4,10)))
:op2 (l2 / level~e.2
:quant-of (e3 / enzyme
:name (n3 / name :op1 "AKT"~e.12)
:ARG3-of p))
:op3 (l3 / level~e.2
:degree-of (a2 / activate-01~e.14
:ARG1~e.15 (p2 / protein
:name (n4 / name :op1 "RalA"~e.16)))))
:mod (a3 / also~e.18)
:time~e.20 (i / introduce-02~e.26
:ARG1 (n8 / nucleic-acid
:name (n5 / name :op1 "siRNA"~e.24)
:mod (e4 / enzyme
:name (n6 / name :op1 "Aurora-A"~e.21,23)))
:ARG2~e.27 (c / cell~e.29
:mod (w / wild-type~e.28))
:condition (i2 / induce-01~e.32
:ARG2 (s3 / small-molecule
:name (n7 / name :op1 "IPTG"~e.31))))
:manner (a4 / accordingly~e.0))
# ::id pmid_2000_3375.152 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Our results confirmed that wild @-@ type @-@ Aurora @-@ A enhance Ras downstream signaling pathways including MEK/ERK , AKT and RalA .
# ::alignments 0-1.1.1 0-1.1.1.r 1-1.1 1-1.1.2 1-1.1.2.r 2-1 3-1.2.r 4-1.2.1.2 6-1.2.1.2 8-1.2.1.1.1 10-1.2.1.1.1 11-1.2 12-1.2.2.2.1.1.1 13-1.2.2.1 14-1.2.2.2 15-1.2.2 16-1.2.2.3 17-1.2.2.3.1.1.1.1 19-1.2.2.3.1.2.1.1 20-1.2.2.3.1 21-1.2.2.3.1.3.1.1
(c / confirm-01~e.2
:ARG0 (t / thing~e.1
:poss~e.0 (w / we~e.0)
:ARG2-of~e.1 (r / result-01~e.1))
:ARG1~e.3 (e2 / enhance-01~e.11
:ARG0 (e4 / enzyme
:name (n3 / name :op1 "Aurora-A"~e.8,10)
:mod (w2 / wild-type~e.4,6))
:ARG1 (p3 / pathway~e.15
:location (d / downstream~e.13)
:ARG0-of (s / signal-07~e.14
:ARG1 (e / enzyme
:name (n / name :op1 "Ras"~e.12)))
:ARG2-of (i / include-91~e.16
:ARG1 (a / and~e.20
:op1 (p / pathway
:name (n2 / name :op1 "MEK/ERK"~e.17))
:op2 (p2 / pathway
:name (n4 / name :op1 "AKT"~e.19))
:op3 (p4 / pathway
:name (n5 / name :op1 "RalA"~e.21)))))))
# ::id pmid_2000_3375.153 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The MEK @/@ ERK pathway is involved in WT cell aggregation
# ::alignments 2-1.1.1.1 4-1.1.1.1 5-1.1 7-1 8-1.2.r 9-1.2.1.1 10-1.2.1 11-1.2
(i / involve-01~e.7
:ARG1 (p / pathway~e.5
:name (n / name :op1 "MEK/ERK"~e.2,4))
:ARG2~e.8 (a / aggregate-01~e.11
:ARG1 (c / cell~e.10
:mod (w / wild-type~e.9))))
# ::id pmid_2000_3375.154 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The involvement of MEK/ERK , PI3K @/@ AKT and RalGDS @/@ RalA signaling pathways in Aurora @-@ A @-@ related cell aggregation ( Fig . 2B , WT + IPTG ) was clarified by treatment of the cells with the following inhibitors : FTI @-@ 277 , a farnesylation inhibitor of Ras ; PD @-@ 98059 , the inhibitor of MEK kinase and LY @-@ 294002 , the inhibitor of PI3K kinase and RalASa94A , a mutant of Ral .
# ::alignments 1-1.1 2-1.1.1.r 3-1.1.1.1.1.1 5-1.1.1.2.1.1 7-1.1.1.2.1.1 8-1.1.1 9-1.1.1.3.1.1 11-1.1.1.3.1.1 12-1.1.1.4 13-1.1.1.1 13-1.1.1.2 13-1.1.1.3 14-1.1.2.r 15-1.1.2.2.1.1.1 17-1.1.2.2.1.1.1 19-1.1.2.2 20-1.1.2.1 21-1.1.2 23-1.1.3.1 26-1.1.3.1.1 30-1.1.1 34-1 35-1.2.r 36-1.2 37-1.2.1.r 39-1.2.1 40-1.2.2.r 42-1.2.2.2 43-1.2.2 43-1.2.2.1 43-1.2.2.1.r 45-1.2.2.3.1.1.1.1 47-1.2.2.3.1.1.1.1 51-1.2.2.3.1.1 51-1.2.2.3.1.1.2 51-1.2.2.3.1.1.2.r 53-1.2.2.3.1.1.2.1.1.1 55-1.2.2.3.1.2.1.1 57-1.2.2.3.1.2.1.1 60-1.2.2.3.1.1 60-1.2.2.3.1.1.2 60-1.2.2.3.1.1.2.r 60-1.2.2.3.1.2 60-1.2.2.3.1.2.2 60-1.2.2.3.1.2.2.r 61-1.2.2.3.1.2.2.1.r 62-1.2.2.3.1.2.2.1.1.1 63-1.2.2.3.1.2.2.1 64-1.2.2.3.1 65-1.2.2.3.1.3.1.1 67-1.2.2.3.1.3.1.1 70-1.2.2.3.1.3 70-1.2.2.3.1.3.2 70-1.2.2.3.1.3.2.r 71-1.2.2.3.1.3.2.1.r 72-1.2.2.3.1.3.2.1.1.1.1 73-1.2.2.3.1.3.2.1.1 74-1.2.2.3.1.3.2.1 75-1.2.2.3.1.3.2.1.2.1.1 78-1.2.2.3.1.3.2.1.2.2 79-1.2.2.3.1.3.2.1.2.2.1.r 80-1.2.2.3.1.3.2.1.2.2.1.1.1
(c / clarify-10~e.34
:ARG1 (i2 / involve-01~e.1
:ARG1~e.2 (a / and~e.8,30
:op1 (p / pathway~e.13
:name (n / name :op1 "MEK/ERK"~e.3))
:op2 (p2 / pathway~e.13
:name (n2 / name :op1 "PI3K/AKT"~e.5,7))
:op3 (p3 / pathway~e.13
:name (n5 / name :op1 "RalGDS/RalA"~e.9,11))
:ARG0-of (s / signal-07~e.12))
:ARG2~e.14 (a2 / aggregate-01~e.21
:ARG1 (c2 / cell~e.20)
:ARG1-of (r / relate-01~e.19
:ARG2 (e2 / enzyme
:name (n6 / name :op1 "Aurora-A"~e.15,17))))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.23 :mod "2B"~e.26)))
:manner~e.35 (t2 / treat-04~e.36
:ARG1~e.37 c2~e.39
:ARG2~e.40 (m / molecular-physical-entity~e.43
:ARG0-of~e.43 (i3 / inhibit-01~e.43)
:ARG1-of (f2 / follow-01~e.42)
:ARG1-of (m2 / mean-01
:ARG2 (a3 / and~e.64
:op1 (s2 / small-molecule~e.51,60
:name (n7 / name :op1 "FTI-277"~e.45,47)
:ARG0-of~e.51,60 (i4 / inhibit-01~e.51,60
:ARG1 (p4 / protein-family
:name (n3 / name :op1 "Ras"~e.53))
:ARG2-of (f3 / farnesylate-01)))
:op2 (s3 / small-molecule~e.60
:name (n8 / name :op1 "PD-98059"~e.55,57)
:ARG0-of~e.60 (i5 / inhibit-01~e.60
:ARG1~e.61 (k / kinase~e.63
:name (n4 / name :op1 "MEK"~e.62))))
:op3 (s4 / small-molecule~e.70
:name (n9 / name :op1 "LY-294002"~e.65,67)
:ARG0-of~e.70 (i6 / inhibit-01~e.70
:ARG1~e.71 (a4 / and~e.74
:op1 (k2 / kinase~e.73
:name (n10 / name :op1 "PI3K"~e.72))
:op1 (p5 / protein
:name (n11 / name :op1 "RalASa94A"~e.75)
:ARG3-of (m6 / mutate-01~e.78
:ARG1~e.79 (p6 / protein
:name (n12 / name :op1 "Ral"~e.80))))))))))))
# ::id pmid_2000_3375.155 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok FTI @-@ 277 restrains Ras protein as a non @-@ farnesylated form and inhibits p @-@ ERK1 @/@ 2 expression dose @-@ dependently but had no effect on p @-@ AKT ( Figure 4A , lanes 2 and 3 ) .
# ::alignments 0-1.1.1.1.1.1 2-1.1.1.1.1.1 3-1.1.1 4-1.1.1.2.1.1 5-1.1.1.2 6-1.1.1.3.r 8-1.1.1.3.1.1 8-1.1.1.3.1.1.r 11-1.1.1.3 12-1.1 13-1.1.2 14-1.1.2.2.1.3 16-1.1.2.2.1.1.1.1 17-1.1.2.2.1 18-1.3.1.1.1 19-1.1.2.2 20-1.1.2.3.1 22-1.1.2.3 23-1 25-1.2.1 25-1.2.1.r 26-1.2 27-1.2.3.r 28-1.2.3.2 30-1.2.3.1.1 32-1.3.1.3 34-1.3.1.3.1 37-1.3.1.1 37-1.3.1.2 38-1.3.1.1.1 39-1.3.1 40-1.3.1.2.1
(c / contrast-01~e.23
:ARG1 (a / and~e.12
:op1 (r / restrain-01~e.3
:ARG0 (s2 / small-molecule
:name (n2 / name :op1 "FTI-277"~e.0,2))
:ARG1 (p / protein-family~e.5
:name (n / name :op1 "Ras"~e.4))
:manner~e.6 (f2 / form~e.11
:ARG1-of (f / farnesylate-01 :polarity~e.8 -~e.8)))
:op2 (i / inhibit-01~e.13
:ARG0 s2
:ARG1 (e / express-03~e.19
:ARG2 (s / slash~e.17
:op1 (e2 / enzyme
:name (n3 / name :op1 "ERK1"~e.16))
:op2 (e3 / enzyme
:name (n4 / name :op1 "ERK2"))
:ARG3-of (p2 / phosphorylate-01~e.14)))
:manner (d / depend-01~e.22
:ARG1 (d2 / dose~e.20))))
:ARG2 (a2 / affect-01~e.26 :polarity~e.25 -~e.25
:ARG0 s2
:ARG1~e.27 (e4 / enzyme
:name (n5 / name :op1 "AKT"~e.30)
:ARG3-of p2~e.28))
:ARG1-of (d3 / describe-01
:ARG0 (a3 / and~e.39
:op1 (l / lane~e.37 :mod 2~e.18,38)
:op2 (l2 / lane~e.37 :mod 3~e.40)
:part-of (f3 / figure~e.32 :mod "4A"~e.34))))
# ::id pmid_2000_3375.156 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok PD @-@ 98059 decreased the phosphorylation of ERK1 @/@ 2 ( p @-@ ERK1 @/@ 2 ) but had no effect on other signaling pathways ( Figure 4A , lanes 4 and 5 ) .
# ::alignments 0-1.1.1.1.1 2-1.1.1.1.1 3-1.1 5-1.1.2 7-1.1.2.1.1.1.1 8-1.1.2.1 11-1.1.2 13-1.1.2.1.1.1.1 14-1.1.2.1 17-1 19-1.2.1 19-1.2.1.r 20-1.2 21-1.2.3.r 22-1.2.3.2 23-1.2.3.1 24-1.2.3 26-1.3.1.3 28-1.3.1.3.1 31-1.3.1.1 31-1.3.1.2 32-1.3.1.1.1 33-1.3.1 34-1.3.1.2.1
(c / contrast-01~e.17
:ARG1 (d / decrease-01~e.3
:ARG0 (s3 / small-molecule
:name (n / name :op1 "PD-98059"~e.0,2))
:ARG1 (p2 / phosphorylate-01~e.5,11
:ARG1 (s / slash~e.8,14
:op1 (e / enzyme
:name (n2 / name :op1 "ERK1"~e.7,13))
:op2 (e2 / enzyme
:name (n3 / name :op1 "ERK2")))))
:ARG2 (a / affect-01~e.20 :polarity~e.19 -~e.19
:ARG0 s3
:ARG1~e.21 (p3 / pathway~e.24
:ARG0-of (s2 / signal-07~e.23)
:mod (o / other~e.22)))
:ARG1-of (d2 / describe-01
:ARG0 (a2 / and~e.33
:op1 (l2 / lane~e.31 :mod 4~e.32)
:op2 (l3 / lane~e.31 :mod 5~e.34)
:part-of (f / figure~e.26 :mod "4A"~e.28))))
# ::id pmid_2000_3375.157 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok LY @-@ 294002 reduced the phosphorylation of AKT ( p @-@ AKT ) but had no effect on another signaling pathway ( Figure 4A , lanes 6 and 7 ) .
# ::alignments 0-1.1.1.1.1 2-1.1.1.1.1 3-1.1 5-1.1.2 7-1.1.2.1.1.1 9-1.1.2 11-1.1.2.1.1.1 13-1 15-1.2.1 15-1.2.1.r 16-1.2 19-1.2.3.1 20-1.2.3 22-1.3.1.3 24-1.3.1.3.1 27-1.3.1.1 27-1.3.1.2 28-1.3.1.1.1 29-1.3.1 30-1.3.1.2.1
(c / contrast-01~e.13
:ARG1 (r / reduce-01~e.3
:ARG0 (s2 / small-molecule
:name (n / name :op1 "LY-294002"~e.0,2))
:ARG1 (p / phosphorylate-01~e.5,9
:ARG1 (e / enzyme
:name (n2 / name :op1 "AKT"~e.7,11))))
:ARG2 (a / affect-01~e.16 :polarity~e.15 -~e.15
:ARG0 s2
:ARG1 (p2 / pathway~e.20
:ARG0-of (s / signal-07~e.19)
:mod (o / other)))
:ARG1-of (d / describe-01
:ARG0 (a2 / and~e.29
:op1 (l2 / lane~e.27 :mod 6~e.28)
:op2 (l3 / lane~e.27 :mod 7~e.30)
:part-of (f / figure~e.22 :mod "4A"~e.24))))
# ::id pmid_2000_3375.158 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok In summary , in WT cells Aurora @-@ A increases the expression of p @-@ ERK1 @/@ 2 in a Ras dependent manner .
# ::alignments 1-1.4 4-1.2.2.1 5-1.2.2 6-1.1.1.1 8-1.1.1.1 9-1 11-1.2 12-1.2.1.r 13-1.2.1.3 15-1.2.1.1.1.1 16-1.2.1 20-1.3.1.1.1 21-1.3 22-1.3.r
(i / increase-01~e.9
:ARG0 (e5 / enzyme
:name (n2 / name :op1 "Aurora-A"~e.6,8))
:ARG1 (e2 / express-03~e.11
:ARG2~e.12 (s2 / slash~e.16
:op1 (e3 / enzyme
:name (n3 / name :op1 "ERK1"~e.15))
:op2 (e4 / enzyme
:name (n4 / name :op1 "ERK2"))
:ARG3-of (p2 / phosphorylate-01~e.13))
:ARG3 (c / cell~e.5
:mod (w / wild-type~e.4)))
:manner~e.22 (d / depend-01~e.21
:ARG1 (e / enzyme
:name (n / name :op1 "Ras"~e.20)))
:ARG2-of (s / summarize-01~e.1))
# ::id pmid_2000_3375.159 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok However , FTI @-@ 277 does not reduce the p @-@ AKT in WT cells co @-@ expressing Ras @ V12 @ and wild @-@ type Aurora @-@ A . Wild @-@ type Aurora @-@ A activates RalA ( Figure 3A and 3B ) and phosphorylates RalA at serine194 to promote cellular transformation and migration [ @ 38 @ ] .
# ::alignments 0-1.1 2-1.1.1.2.1.1 4-1.1.1.2.1.1 6-1.1.1.1 6-1.1.1.1.r 7-1.1.1 9-1.1.1.3.2 11-1.1.1.3.1.1 12-1.1.1.4.r 13-1.1.1.4.1 14-1.1.1.4 18-1.1.1.4.2.1.1.1.1 20-1.1.1.4.2.1.1.2.1 22-1.1.1.4.2.1 23-1.1.1.4.2.1.2.2 24-1.1.1.4.2.1.2.2 25-1.1.1.4.2.1.2.2 26-1.1.1.4.2.1.2.1.1 28-1.1.1.4.2.1.2.1.1 30-1.1.1.4.2.1.2.2 31-1.1.1.4.2.1.2.2 32-1.1.1.4.2.1.2.2 33-1.2.1.1.1.1 35-1.2.1.1.1.1 36-1.2.1 37-1.2.1.2.1.1 39-1.2.1.3.1.1 39-1.2.1.3.1.2 41-1.2.1.3.1.1.1 43-1.2.1.3.1 45-1.2.1.3.1.2.1 48-1.2 49-1.2.2 50-1.2.1.2.1.1 54-1.2.2.3 55-1.2.2.3.2.1.1 56-1.2.2.3.2.1 57-1.2.2.3.2 58-1.2.2.3.2.2 61-1.2.3.1.1.1
(m / multi-sentence
:snt1 (h / have-concession-91~e.0
:ARG1 (r / reduce-01~e.7 :polarity~e.6 -~e.6
:ARG0 (s / small-molecule
:name (n2 / name :op1 "FTI-277"~e.2,4))
:ARG1 (e2 / enzyme
:name (n3 / name :op1 "AKT"~e.11)
:ARG3-of (p / phosphorylate-01~e.9))
:location~e.12 (c / cell~e.14
:mod (w / wild-type~e.13)
:ARG3-of (c2 / coexpress-01
:ARG2 (a / and~e.22
:op1 (e / enzyme
:name (n / name :op1 "Ras"~e.18)
:ARG2-of (m3 / mutate-01 :value "V12"~e.20))
:op2 (e3 / enzyme
:name (n4 / name :op1 "Aurora-A"~e.26,28)
:mod w~e.23,24,25,30,31,32))))))
:snt2 (a2 / and~e.48
:op1 (a3 / activate-01~e.36
:ARG0 (e4 / enzyme
:name (n5 / name :op1 "Aurora-A"~e.33,35))
:ARG1 (p4 / protein
:name (n6 / name :op1 "RalA"~e.37,50))
:ARG1-of (d / describe-01
:ARG0 (a4 / and~e.43
:op1 (f / figure~e.39 :mod "3A"~e.41)
:op2 (f2 / figure~e.39 :mod "3B"~e.45))))
:op2 (p5 / phosphorylate-01~e.49
:ARG1 (a5 / amino-acid :mod 194
:name (n7 / name :op1 "serine")
:part-of p4)
:ARG2 e4
:purpose (p6 / promote-02~e.54
:ARG0 e4
:ARG1 (a6 / and~e.57
:op1 (t / transform-01~e.56
:ARG1 (c3 / cell~e.55))
:op2 (m4 / migrate-01~e.58
:ARG0 c3))))
:ARG1-of (d2 / describe-01
:ARG0 (p7 / publication
:ARG1-of (c4 / cite-01 :ARG2 38~e.61)))))
# ::id pmid_2000_3375.160 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To reveal the role of RalA phosphorylation at ser194 in Aurora @-@ A induced RalA activation in WT cells , the mutants RalAS183A or RalAS194A were transiently transfected into WT cells and the RalA activity was evaluated .
# ::alignments 1-1.3 5-1.3.1.1.1.3 6-1.3.1.1 10-1.3.1.2.2.1.1.1 12-1.3.1.2.2.1.1.1 13-1.3.1.2.2 14-1.3.1.2.1 15-1.3.1.2 17-1.1.1.1 18-1.1.1 21-1.1.2.3 22-1.1.2.1.1.1 23-1.1.2 24-1.1.2.2.1.1 26-1.1.3 27-1.1 29-1.1.1.1 30-1.1.1 31-1 33-1.2.1.1.1.1 34-1.2.1 36-1.2
(a / and~e.31
:op1 (t / transfect-01~e.27
:ARG1 (c / cell~e.18,30
:mod (w / wild-type~e.17,29))
:ARG2 (o / or~e.23
:op1 (p2 / protein
:name (n / name :op1 "RalAS183A"~e.22))
:op2 (p3 / protein
:name (n2 / name :op1 "RalAS194A"~e.24))
:ARG2-of (m / mutate-01~e.21))
:ARG1-of (t2 / transient-02~e.26))
:op2 (e / evaluate-01~e.36
:ARG1 (a2 / activity-06~e.34
:ARG0 (p4 / protein
:name (n3 / name :op1 "RalA"~e.33))))
:purpose (r / reveal-01~e.1
:ARG1 (p5 / play-08
:ARG0 (p / phosphorylate-01~e.6
:ARG1 (a3 / amino-acid :mod 194
:name (n4 / name :op1 "serine")
:part-of p4~e.5))
:ARG1 (a4 / activate-01~e.15
:ARG1 p4~e.14
:ARG2-of (i / induce-01~e.13
:ARG0 (e2 / enzyme
:name (n5 / name :op1 "Aurora-A"~e.10,12))))
:location c)))
# ::id pmid_2000_3375.161 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Consistent with a previous report [ @ 38 @ ] , only RalAS194A could reduce the Ral A activity ( Figure 4B , lane 3 ) .
# ::alignments 0-1 1-1.2.r 3-1.2.1 4-1.2 7-1.2.2.1.1.1 11-1.1.1.1.2 12-1.1.1.1.1.1 13-1.1 14-1.1.1 18-1.1.1.2 20-1.1.2.1.2 22-1.1.2.1.2.1 25-1.1.2.1 26-1.1.2.1.1
(c / consistent-01~e.0
:ARG1 (p2 / possible-01~e.13
:ARG1 (r / reduce-01~e.14
:ARG0 (p3 / protein
:name (n / name :op1 "RalAS194A"~e.12)
:mod (o / only~e.11))
:ARG1 (a / activity-06~e.18
:ARG0 (p4 / protein
:name (n2 / name :op1 "RalA"))))
:ARG1-of (d2 / describe-01
:ARG0 (l / lane~e.25 :mod 3~e.26
:part-of (f / figure~e.20 :mod "4B"~e.22))))
:ARG2~e.1 (r2 / report~e.4
:time (p / previous~e.3)
:ARG1-of (d / describe-01
:ARG0 (p5 / publication
:ARG1-of (c2 / cite-01 :ARG2 38~e.7)))))
# ::id pmid_2000_3375.162 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok To determine which signaling pathway is involved in the aggregation of WT cells during Ras @ V12 @ overexpression , we first demonstrated that Aurora @-@ A induced cell aggregation was blocked by Aurora @-@ A specific small interfering RNA ( Figure 4C ) .
# ::alignments 1-1.4 3-1.4.2.2.1 4-1.4.2.2 6-1.4.2 7-1.4.2.3.r 9-1.4.2.3 10-1.4.2.3.1.r 11-1.4.2.3.1.1 12-1.4.2.3.1 13-1.4.2.4.r 14-1.4.2.4.1.1.1 16-1.4.2.4.1.2.1 18-1.4.2.4 20-1.1 21-1.3 22-1 23-1.2.r 24-1.2.1.2.1.1.1 26-1.2.1.2.1.1.1 27-1.2.1.2 28-1.2.1.1 29-1.2.1 31-1.2 32-1.2.2.r 33-1.2.2.2.1 34-1.2.2.2.1 35-1.2.2.2.1 36-1.2.2 36-1.2.2.2 36-1.2.2.2.r 37-1.2.2.1.1 38-1.2.2.1.2 39-1.2.2.1.3 41-1.5.1 43-1.5.1.1
(d / demonstrate-01~e.22
:ARG0 (w / we~e.20)
:ARG1~e.23 (b / block-01~e.31
:ARG1 (a / aggregate-01~e.29
:ARG1 (c / cell~e.28)
:ARG2-of (i / induce-01~e.27
:ARG0 (e2 / enzyme
:name (n2 / name :op1 "Aurora-A"~e.24,26))))
:ARG2~e.32 (n4 / nucleic-acid~e.36
:name (n3 / name :op1 "small"~e.37 :op2 "interfering"~e.38 :op3 "RNA"~e.39)
:ARG1-of~e.36 (s / specific-02~e.36
:ARG2 e2~e.33,34,35)))
:time (f / first~e.21)
:purpose (d2 / determine-01~e.1
:ARG0 w
:ARG1 (i2 / involve-01~e.6 :mode interrogative
:ARG1 (p2 / pathway~e.4
:ARG0-of (s2 / signal-07~e.3))
:ARG2~e.7 (a2 / aggregate-01~e.9
:ARG1~e.10 (c2 / cell~e.12
:mod (w3 / wild-type~e.11)))
:time~e.13 (o2 / overexpress-01~e.18
:ARG1 (e / enzyme
:name (n / name :op1 "Ras"~e.14)
:ARG2-of (m / mutate-01 :value "V12"~e.16)))))
:ARG1-of (d3 / describe-01
:ARG0 (f2 / figure~e.41 :mod "4C"~e.43)))
# ::id pmid_2000_3375.163 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok The WT cells were treated with FTI @-@ 277 , PD @-@ 98059 or LY @-@ 294002 for 24 h and cell aggregation was observed .
# ::alignments 1-1.1.1.1 2-1.1.1 4-1.1 5-1.1.2.r 6-1.1.2.1.1.1 8-1.1.2.1.1.1 10-1.1.2.2.1.1 12-1.1.2.2.1.1 13-1.1.2 14-1.1.2.3.1.1 16-1.1.2.3.1.1 17-1.1.3.r 18-1.1.3.1 19-1.1.3.2 21-1.1.1 22-1.2.1 24-1.2
(a / and
:op1 (t / treat-04~e.4
:ARG1 (c / cell~e.2,21
:mod (w / wild-type~e.1))
:ARG2~e.5 (o / or~e.13
:op1 (s / small-molecule
:name (n / name :op1 "FTI-277"~e.6,8))
:op2 (s2 / small-molecule
:name (n2 / name :op1 "PD-98059"~e.10,12))
:op3 (s3 / small-molecule
:name (n3 / name :op1 "LY-294002"~e.14,16)))
:duration~e.17 (t2 / temporal-quantity :quant 24~e.18
:unit (h / hour~e.19)))
:op2 (o2 / observe-01~e.24
:ARG1 (a2 / aggregate-01~e.22
:ARG1 c)))
# ::id pmid_2000_3375.164 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Both FTI @-@ 277 and PD98059 reversed the aggregation of WT cells , whereas LY @-@ 294002 showed no effect on cell aggregation ( Figure 4C ) .
# ::alignments 1-1.1.1.1.1.1 3-1.1.1.1.1.1 4-1.1.1 5-1.1.1.2.1.1 6-1.1 8-1.1.2 9-1.1.2.1.r 10-1.1.2.1.1 11-1.1.2.1 13-1 14-1.2.1.1.1 16-1.2.1.1.1 17-1.2 18-1.2.2.1 18-1.2.2.1.r 19-1.2.2 20-1.2.2.3.r 21-1.2.2.3 22-1.2.2.3 24-1.3.1 26-1.3.1.1
(c / contrast-01~e.13
:ARG1 (r / reverse-01~e.6
:ARG0 (a / and~e.4
:op1 (s3 / small-molecule
:name (n / name :op1 "FTI-277"~e.1,3))
:op2 (s4 / small-molecule
:name (n2 / name :op1 "PD98059"~e.5)))
:ARG1 (a2 / aggregate-01~e.8
:ARG1~e.9 (c2 / cell~e.11
:mod (w / wild-type~e.10))))
:ARG2 (s / show-01~e.17
:ARG0 (s2 / small-molecule
:name (n3 / name :op1 "LY-294002"~e.14,16))
:ARG1 (a3 / affect-01~e.19 :polarity~e.18 -~e.18
:ARG0 s2
:ARG1~e.20 a2~e.21,22))
:ARG1-of (d / describe-01
:ARG0 (f / figure~e.24 :mod "4C"~e.26)))
# ::id pmid_2000_3375.165 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Because mutant RalAS194A was unable to block cell aggregation , its role in Aurora @-@ A induced cell aggregation was excluded ( Figure 4C ) .
# ::alignments 0-1.2 1-1.1.1 1-1.1.1.2 1-1.1.1.2.r 2-1.1.1.1.1 4-1.2.1.1 6-1.2.1.3 7-1.1.2.1 8-1.1.2 13-1.1.2.2.1.1.1 15-1.1.2.2.1.1.1 16-1.1.2.2 17-1.1.2.1 18-1.1.2 20-1
(e / exclude-01~e.20
:ARG1 (p / play-08
:ARG0 (p2 / protein~e.1
:name (n / name :op1 "RalAS194A"~e.2)
:ARG2-of~e.1 (m / mutate-01~e.1))
:ARG1 (a / aggregate-01~e.8,18
:ARG1 (c / cell~e.7,17)
:ARG2-of (i / induce-01~e.16
:ARG0 (e2 / enzyme
:name (n2 / name :op1 "Aurora-A"~e.13,15)))))
:ARG1-of (c2 / cause-01~e.0
:ARG0 (c3 / capable-01 :polarity -~e.4
:ARG1 p2
:ARG2 (b / block-01~e.6
:ARG0 p2
:ARG1 a))))
# ::id pmid_2000_3375.166 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Taken together , the Ras/MEK/ERK signaling pathway but not the PI3K @/@ AKT or RalGDS @/@ RalA pathway is responsible for Aurora @-@ A induced cell aggregation .
# ::alignments 0-1.2 1-1.2.2 4-1.1.1.1.1.1 5-1.1.1.1.2 6-1.1.1.1 7-1.1 8-1.1.2.1 8-1.1.2.1.r 10-1.1.2.2.1.1.1 12-1.1.2.2.1.1.1 13-1.1.2.2 14-1.1.2.2.2.1.1 16-1.1.2.2.2.1.1 17-1.1.1.1 17-1.1.2.2.1 17-1.1.2.2.2 19-1.1.1 19-1.1.2 20-1.1.1.2.r 21-1.1.1.2.2.1.1.1 23-1.1.1.2.2.1.1.1 24-1.1.1.2.2 25-1.1.1.2.1 26-1.1.1.2
(h / have-condition-91
:ARG1 (c / contrast-01~e.7
:ARG1 (r / responsible-01~e.19
:ARG0 (p2 / pathway~e.6,17
:name (n2 / name :op1 "Ras/MEK/ERK"~e.4)
:ARG0-of (s / signal-07~e.5))
:ARG1~e.20 (a / aggregate-01~e.26
:ARG1 (c2 / cell~e.25)
:ARG2-of (i / induce-01~e.24
:ARG0 (e / enzyme
:name (n3 / name :op1 "Aurora-A"~e.21,23)))))
:ARG2 (r2 / responsible-01~e.19 :polarity~e.8 -~e.8
:ARG0 (o / or~e.13
:op1 (p / pathway~e.17
:name (n / name :op1 "PI3K/AKT"~e.10,12))
:op2 (p4 / pathway~e.17
:name (n4 / name :op1 "RalGDS/RalA"~e.14,16)))
:ARG1 a))
:ARG2 (t / take-01~e.0
:ARG1 p2
:mod (t2 / together~e.1)))