;PMID: 12149262 ;source_file_2854.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..60] = [t:0..60] ;1)sentence:[e:65..231] = [t:65..231] ;2)section:[e:235..312] = [t:235..312] ;3)section:[e:316..409] = [t:316..409] ;4)sentence:[e:413..533] = [t:413..533] ;5)sentence:[e:534..637] = [t:534..637] ;6)sentence:[e:638..740] = [t:638..740] ;7)sentence:[e:741..819] = [t:741..819] ;8)sentence:[e:820..929] = [t:820..929] ;9)sentence:[e:930..1091] = [t:930..1091] ;10)sentence:[e:1092..1306] = [t:1092..1306] ;11)section:[e:1310..1355] = [t:1310..1355] ;section 0 Span:0..60 ;J Biol Chem. 2002 Oct 4;277(40):37788-97. Epub 2002 Jul 30. (SEC (FRAG (NNP:[0..1] J) (NNP:[2..6] Biol) (NNP:[7..11] Chem) (.:[11..12] .) ('':[14..18] 2002) (NNP:[19..22] Oct) (CD:[23..28] 4;277) (-LRB-:[28..29] -LRB-) (CD:[29..31] 40) (-RRB-:[31..32] -RRB-) (::[32..33] :) (CD:[33..37] 3778) (CD:[37..38] 8) (HYPH:[38..39] -) (CD:[39..41] 97) (.:[41..42] .) (NNP:[43..47] Epub) (VBD:[48..52] 2002) (NNP:[53..56] Jul) (CD:[57..59] 30) (.:[59..60] .))) ;sentence 1 Span:65..231 ;The adaptor protein Nck-1 couples the netrin-1 receptor DCC (deleted in ;colorectal cancer) to the activation of the small GTPase Rac1 through an ;atypical mechanism. ;[85..90]:gene-protein:"Nck-1" ;[103..120]:gene-protein:"netrin-1 receptor" ;[121..124]:gene-protein:"DCC" ;[138..155]:malignancy-type:"colorectal cancer" ;[188..194]:gene-protein:"GTPase" ;[195..199]:gene-protein:"Rac1" (SENT (S-HLN (NP-SBJ (NP (DT:[65..68] The) (NN:[69..76] adaptor) (NN:[77..84] protein)) (NP (NN:[85..90] Nck-1))) (VP (VBZ:[91..98] couples) (NP (NP (NP (DT:[99..102] the) (NN:[103..111] netrin-1) (NN:[112..120] receptor)) (NP (NN:[121..124] DCC))) (PRN (-LRB-:[125..126] -LRB-) (VP (VBN:[126..133] deleted) (NP (-NONE-:[133..133] *)) (PP (IN:[134..136] in) (NP (JJ:[138..148] colorectal) (NN:[149..155] cancer)))) (-RRB-:[155..156] -RRB-))) (PP (TO:[157..159] to) (NP (NP (DT:[160..163] the) (NN:[164..174] activation)) (PP (IN:[175..177] of) (NP (DT:[178..181] the) (JJ:[182..187] small) (NN:[188..194] GTPase) (NN:[195..199] Rac1))))) (PP-MNR (IN:[200..207] through) (NP (DT:[208..210] an) (JJ:[212..220] atypical) (NN:[221..230] mechanism)))) (.:[230..231] .))) ;section 2 Span:235..312 ;Li X, Meriane M, Triki I, Shekarabi M, Kennedy TE, Larose L, Lamarche-Vane ;N. (SEC (FRAG (NNP:[235..237] Li) (NNP:[238..239] X) (,:[239..240] ,) (NNP:[241..248] Meriane) (NNP:[249..251] M,) (NNP:[252..257] Triki) (NNP:[258..259] I) (,:[259..260] ,) (NNP:[261..270] Shekarabi) (NNP:[271..273] M,) (NNP:[274..281] Kennedy) (NNP:[282..284] TE) (,:[284..285] ,) (NNP:[286..292] Larose) (NNP:[293..295] L,) (NNP:[296..305] Lamarche-) (NNP:[305..309] Vane) (NNP:[310..311] N) (.:[311..312] .))) ;section 3 Span:316..409 ;Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec ;H3A 2B2, Canada. (SEC (FRAG (NNP:[316..326] Department) (IN:[327..329] of) (NNP:[330..337] Anatomy) (CC:[338..341] and) (NNP:[342..346] Cell) (NNP:[347..354] Biology) (,:[354..355] ,) (NNP:[356..362] McGill) (NNP:[363..373] University) (,:[373..374] ,) (NNP:[375..383] Montreal) (,:[383..384] ,) (NNP:[385..391] Quebec) (NNP:[392..395] H3A) (NNP:[397..400] 2B2) (,:[400..401] ,) (NNP:[402..408] Canada) (.:[408..409] .))) ;sentence 4 Span:413..533 ;Netrins are a family of secreted proteins that guide the migration of cells ;and axonal growth cones during development. ;[413..420]:gene-protein:"Netrins" (SENT (S (NP-SBJ (NNS:[413..420] Netrins)) (VP (VBP:[421..424] are) (NP-PRD (NP (DT:[425..426] a) (NN:[427..433] family)) (PP (IN:[434..436] of) (NP (NP (VBN:[437..445] secreted) (NNS:[446..454] proteins)) (SBAR (WHNP-1 (WDT:[455..459] that)) (S (NP-SBJ-1 (-NONE-:[459..459] *T*)) (VP (VBP:[460..465] guide) (NP (NP (DT:[466..469] the) (NN:[470..479] migration)) (PP (IN:[480..482] of) (NP (NP (NNS:[483..488] cells)) (CC:[489..492] and) (NP (JJ:[494..500] axonal) (NN:[501..507] growth) (NNS:[508..513] cones)))) (PP-TMP (IN:[514..520] during) (NP (NN:[521..532] development))))))))))) (.:[532..533] .))) ;sentence 5 Span:534..637 ;DCC (deleted in colorectal cancer) is a receptor for netrin-1 implicated in ;mediating these responses. ;[534..537]:gene-protein:"DCC" ;[550..567]:malignancy-type:"colorectal cancer" ;[588..596]:gene-protein:"netrin-1" (SENT (S (NP-SBJ (NN:[534..537] DCC) (PRN (-LRB-:[538..539] -LRB-) (VP (VBN:[539..546] deleted) (NP (-NONE-:[546..546] *)) (PP (IN:[547..549] in) (NP (JJ:[550..560] colorectal) (NN:[561..567] cancer)))) (-RRB-:[567..568] -RRB-))) (VP (VBZ:[569..571] is) (NP-PRD (NP (NP (DT:[572..573] a) (NN:[575..583] receptor)) (PP (IN:[584..587] for) (NP (NN:[588..596] netrin-1)))) (VP (VBN:[597..607] implicated) (NP (-NONE-:[607..607] *)) (PP (IN:[608..610] in) (S-NOM (NP-SBJ (-NONE-:[610..610] *)) (VP (VBG:[611..620] mediating) (NP (DT:[621..626] these) (NNS:[627..636] responses)))))))) (.:[636..637] .))) ;sentence 6 Span:638..740 ;Here, we show that DCC interacts constitutively with the SH3/SH2 adaptor Nck ;in commissural neurons. ;[658..661]:gene-protein:"DCC" ;[712..715]:gene-protein:"Nck" (SENT (S (ADVP (RB:[638..642] Here)) (,:[642..643] ,) (NP-SBJ (PRP:[644..646] we)) (VP (VBP:[647..651] show) (SBAR (IN:[653..657] that) (S (NP-SBJ (NN:[658..661] DCC)) (VP (VBZ:[662..671] interacts) (ADVP (RB:[672..686] constitutively)) (PP (IN:[687..691] with) (NP (NP (DT:[692..695] the) (NML (NN:[696..699] SH3) (SYM:[699..700] /) (NN:[700..703] SH2)) (NN:[704..711] adaptor)) (NP (NN:[712..715] Nck)))) (PP (IN:[716..718] in) (NP (JJ:[719..730] commissural) (NNS:[732..739] neurons))))))) (.:[739..740] .))) ;sentence 7 Span:741..819 ;This interaction is direct and requires the SH3 but not SH2 domains of ;Nck-1. ;[813..818]:gene-protein:"Nck-1" (SENT (S (NP-SBJ (DT:[741..745] This) (NN:[746..757] interaction)) (VP (VP (VBZ:[758..760] is) (ADJP-PRD (JJ:[761..767] direct))) (CC:[768..771] and) (VP (VBZ:[772..780] requires) (NP (NP (DT:[781..784] the) (NML (NML (NN:[785..788] SH3) (NML-1 (-NONE-:[788..788] *P*))) (CONJP (CC:[789..792] but) (RB:[793..796] not)) (NML-1 (NN:[797..800] SH2) (NML (NNS:[801..808] domains))))) (PP (IN:[809..811] of) (NP (NN:[813..818] Nck-1)))))) (.:[818..819] .))) ;sentence 8 Span:820..929 ;Moreover, both DCC and Nck-1 associate with the actin cytoskeleton, and this ;association is mediated by DCC. ;[835..838]:gene-protein:"DCC" ;[843..848]:gene-protein:"Nck-1" ;[868..873]:gene-protein:"actin" ;[925..928]:gene-protein:"DCC" (SENT (S (S (ADVP (RB:[820..828] Moreover)) (,:[828..829] ,) (NP-SBJ (CC:[830..834] both) (NP (NN:[835..838] DCC)) (CC:[839..842] and) (NP (NN:[843..848] Nck-1))) (VP (VBP:[849..858] associate) (PP-CLR (IN:[859..863] with) (NP (DT:[864..867] the) (NN:[868..873] actin) (NN:[874..886] cytoskeleton))))) (,:[886..887] ,) (CC:[888..891] and) (S (NP-SBJ-1 (DT:[893..897] this) (NN:[898..909] association)) (VP (VBZ:[910..912] is) (VP (VBN:[913..921] mediated) (NP-1 (-NONE-:[921..921] *)) (PP (IN:[922..924] by) (NP-LGS (NN:[925..928] DCC)))))) (.:[928..929] .))) ;sentence 9 Span:930..1091 ;A dominant negative Nck-1 inhibits the ability of DCC to induce neurite ;outgrowth in N1E-115 cells and to activate Rac1 in fibroblasts in response ;to netrin-1. ;[950..955]:gene-protein:"Nck-1" ;[981..984]:gene-protein:"DCC" ;[1046..1050]:gene-protein:"Rac1" ;[1082..1090]:gene-protein:"netrin-1" (SENT (S (NP-SBJ (DT:[930..931] A) (JJ:[932..940] dominant) (JJ:[941..949] negative) (NN:[950..955] Nck-1)) (VP (VBZ:[956..964] inhibits) (NP (NP (DT:[965..968] the) (NN:[970..977] ability) (S-1 (-NONE-:[977..977] *ICH*))) (PP (IN:[978..980] of) (NP (NN:[981..984] DCC))) (S-1 (NP-SBJ (-NONE-:[984..984] *)) (VP (VP (TO:[985..987] to) (VP (VB:[988..994] induce) (NP (NN:[995..1002] neurite) (NN:[1003..1012] outgrowth)) (PP-LOC (IN:[1013..1015] in) (NP (NN:[1016..1023] N1E-115) (NNS:[1024..1029] cells))))) (CC:[1030..1033] and) (VP (TO:[1034..1036] to) (VP (VB:[1037..1045] activate) (NP (NN:[1046..1050] Rac1)) (PP-LOC (IN:[1052..1054] in) (NP (NNS:[1055..1066] fibroblasts))) (PP (IN:[1067..1069] in) (NP (NP (NN:[1070..1078] response)) (PP (TO:[1079..1081] to) (NP (NN:[1082..1090] netrin-1))))))))))) (.:[1090..1091] .))) ;sentence 10 Span:1092..1306 ;These studies provide evidence for an important role of mammalian Nck-1 in a ;novel signaling pathway from an extracellular guidance cue to changes in the ;actin-based cytoskeleton responsible for axonal guidance. ;[1159..1164]:gene-protein:"Nck-1" ;[1248..1253]:gene-protein:"actin" (SENT (S (NP-SBJ (DT:[1092..1097] These) (NNS:[1098..1105] studies)) (VP (VBP:[1106..1113] provide) (NP (NP (NN:[1114..1122] evidence)) (PP (IN:[1123..1126] for) (NP (NP (DT:[1127..1129] an) (JJ:[1131..1140] important) (NN:[1141..1145] role)) (PP (IN:[1146..1148] of) (NP (JJ:[1149..1158] mammalian) (NN:[1159..1164] Nck-1))) (PP (IN:[1165..1167] in) (NP (DT:[1168..1169] a) (JJ:[1170..1175] novel) (NN:[1176..1185] signaling) (NN:[1186..1193] pathway))))) (PP (IN:[1194..1198] from) (NP (NP (DT:[1199..1201] an) (JJ:[1203..1216] extracellular) (NN:[1217..1225] guidance) (NN:[1226..1229] cue)) (PP (TO:[1230..1232] to) (NP (NP (NNS:[1233..1240] changes)) (PP (IN:[1241..1243] in) (NP (NP (DT:[1244..1247] the) (ADJP (NN:[1248..1253] actin) (HYPH:[1253..1254] -) (VBN:[1254..1259] based)) (NN:[1260..1272] cytoskeleton)) (ADJP (JJ:[1274..1285] responsible) (PP (IN:[1286..1289] for) (NP (JJ:[1290..1296] axonal) (NN:[1297..1305] guidance)))))))))))) (.:[1305..1306] .))) ;section 11 Span:1310..1355 ;PMID: 12149262 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1310..1314] PMID) (::[1314..1315] :) (CD:[1316..1324] 12149262) (NN:[1325..1326] -LSB-) (NNP:[1326..1332] PubMed) (::[1333..1334] -) (NN:[1335..1342] indexed) (IN:[1343..1346] for) (NNP:[1347..1355] MEDLINE-RSB-)))