Premium
The coupling of α 6 β 4 integrin to Ras–MAP kinase pathways mediated by Shc controls keratinocyte proliferation
Author(s) -
Mainiero Fabrizio,
Murgia Chiara,
Wary Kishore K.,
Curatola Anna Maria,
Pepe Angela,
Blumemberg Miroslav,
Westwick John K.,
Der Channing J.,
Giancotti Filippo G.
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.9.2365
Subject(s) - biology , integrin , keratinocyte , microbiology and biotechnology , signal transduction , coupling (piping) , focal adhesion , kinase , biochemistry , cell , in vitro , materials science , metallurgy
The signaling pathways linking integrins to nuclear events are incompletely understood. We have examined intracellular signaling by the α 6 β 4 integrin, a laminin receptor expressed in basal keratinocytes and other cells. Ligation of α 6 β 4 in primary human keratinocytes caused tyrosine phosphorylation of Shc, 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 α 3 β 1 and α 2 β 1 did not cause these events. While the stimulation of Erk by α 6 β 4 was suppressed by dominant‐negative Shc, Ras and RhoA, the activation of Jnk was inhibited by dominant‐negative Ras and Rac1 and by the phosphoinositide 3‐kinase inhibitor Wortmannin. Adhesion mediated by α 6 β 4 induced transcription from the Fos serum response element and promoted cell cycle progression in response to mitogens. In contrast, α 3 β 1 ‐ and α 2 β 1 ‐dependent adhesion did not induce these events. These findings suggest that the coupling of α 6 β 4 integrin to the control of cell cycle progression mediated by Shc regulates the proliferation of basal keratinocytes and possibly other cells which are in contact with the basement membrane in vivo .