The coupling of alpha(6)beta(4) integrin to Ras-MAP kinase pathways mediated by Shc controls keratinocyte proliferation

被引:289
作者
Mainiero, F
Murgia, C
Wary, KK
Curatola, AM
Pepe, A
Blumemberg, M
Westwick, JK
Der, CJ
Giancotti, FG
机构
[1] NYU,SCH MED,KAPLAN CANC CTR,DEPT DERMATOL,NEW YORK,NY 10016
[2] UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,DEPT PHARMACOL,CHAPEL HILL,NC 27599
[3] NYU,SCH MED,KAPLAN CANC CTR,DEPT PATHOL,NEW YORK,NY 10016
关键词
integrins; keratinocytes; MAP kinase; Ras; Shc;
D O I
10.1093/emboj/16.9.2365
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The signaling pathways linking integrins to nuclear events are incompletely understood, We have examined intracellular signaling by the alpha(6) beta(4) integrin, a laminin receptor expressed in basal keratinocytes and other cells, Ligation of alpha(6) beta(4) in primary human keratinocytes caused tyrosine phosphorylation of She, recruitment of Grb2, activation of Ras and stimulation of the MAP kinases Erk and Jnk. In contrast, ligation of the laminin- and collagen-binding integrins alpha(3) beta(1) and alpha(2) beta(1) did not cause these events, While the stimulation of Erk by alpha(6) beta(4) was suppressed by dominant-negative Shc, Pas and RhoA, the activation of Jnk was inhibited by dominant-negative Pas and Rad and by the phosphoinositide 3-kinase inhibitor Wortmannin. Adhesion mediated by alpha(6) beta(4) induced transcription from the Fos serum response element and promoted a:ll cycle progression in response to mitogens, In contrast, alpha(3) beta(1)- and alpha(2) beta(1)-dependent adhesion did not induce these events, These findings suggest that the coupling of alpha(6) beta(4) integrin to the control of cell cycle progression mediated by She regulates the proliferation of basal keratinocytes and possibly other cells which are in contact with the basement membrane in vivo.
引用
收藏
页码:2365 / 2375
页数:11
相关论文
共 59 条
[1]  
ADAMS JC, 1993, DEVELOPMENT, V117, P1183
[2]   SH3 DOMAINS DIRECT CELLULAR-LOCALIZATION OF SIGNALING MOLECULES [J].
BARSAGI, D ;
ROTIN, D ;
BATZER, A ;
MANDIYAN, V ;
SCHLESSINGER, J .
CELL, 1993, 74 (01) :83-91
[3]  
BRASIER AR, 1989, BIOTECHNIQUES, V7, P1116
[4]   EPILIGRIN, A NEW CELL-ADHESION LIGAND FOR INTEGRIN ALPHA-3-BETA-1 IN EPITHELIAL BASEMENT-MEMBRANES [J].
CARTER, WG ;
RYAN, MC ;
GAHR, PJ .
CELL, 1991, 65 (04) :599-610
[5]   THE ROLE OF INTEGRINS ALPHA-2-BETA-1 AND ALPHA-3-BETA-1 IN CELL CELL AND CELL SUBSTRATE ADHESION OF HUMAN EPIDERMAL-CELLS [J].
CARTER, WG ;
WAYNER, EA ;
BOUCHARD, TS ;
KAUR, P .
JOURNAL OF CELL BIOLOGY, 1990, 110 (04) :1387-1404
[6]   DISTINCT FUNCTIONS FOR INTEGRINS ALPHA-3-BETA-1 IN FOCAL ADHESIONS AND ALPHA-6-BETA-4 BULLOUS PEMPHIGOID ANTIGEN IN A NEW STABLE ANCHORING CONTACT (SAC) OF KERATINOCYTES - RELATION TO HEMIDESMOSOMES [J].
CARTER, WG ;
KAUR, P ;
GIL, SG ;
GAHR, PJ ;
WAYNER, EA .
JOURNAL OF CELL BIOLOGY, 1990, 111 (06) :3141-3154
[7]   INTEGRINS AND SIGNAL-TRANSDUCTION PATHWAYS - THE ROAD TAKEN [J].
CLARK, EA ;
BRUGGE, JS .
SCIENCE, 1995, 268 (5208) :233-239
[8]   JNK1 - A PROTEIN-KINASE STIMULATED BY UV-LIGHT AND HA-RAS THAT BINDS AND PHOSPHORYLATES THE C-JUN ACTIVATION DOMAIN [J].
DERIJARD, B ;
HIBI, M ;
WU, IH ;
BARRETT, T ;
SU, B ;
DENG, TL ;
KARIN, M ;
DAVIS, RJ .
CELL, 1994, 76 (06) :1025-1037
[9]   beta 4 integrin is required for hemidesmosome formation, cell adhesion and cell survival [J].
Dowling, J ;
Yu, QC ;
Fuchs, E .
JOURNAL OF CELL BIOLOGY, 1996, 134 (02) :559-572
[10]   AXONAL REGULATION OF SCHWANN-CELL INTEGRIN EXPRESSION SUGGESTS A ROLE FOR ALPHA-6-BETA-4 IN MYELINATION [J].
EINHEBER, S ;
MILNER, TA ;
GIANCOTTI, F ;
SALZER, JL .
JOURNAL OF CELL BIOLOGY, 1993, 123 (05) :1223-1236