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- Title
The coupling of α<sub>6</sub>β<sub>4</sub> integrin to Ras–MAP kinase pathways mediated by Shc controls keratinocyte proliferation.
- Authors
Mainiero, Fabrizio; Murgia, Chiara; Wary, Kishore K.; Curatola, Anna Maria; Pepe, Angela; Blumemberg, Miroslav; Westwick, John K.; Der, Channing J.; Giancotti, Filippo G.
- Abstract
The signaling pathways linking integrins to nuclear events are incompletely understood. We have examined intracellular signaling by the α6β4 integrin, a laminin receptor expressed in basal keratinocytes and other cells. Ligation of α6β4 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 α3β1 and α2β1 did not cause these events. While the stimulation of Erk by α6β4 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 α6β4induced transcription from the Fos serum response element and promoted cell cycle progression in response to mitogens. In contrast, α3β1- and α2β1-dependent adhesion did not induce these events. These findings suggest that the coupling of α6β4 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.
- Publication
EMBO Journal, 1997, Vol 16, Issue 9, p2365
- ISSN
0261-4189
- Publication type
Academic Journal
- DOI
10.1093/emboj/16.9.2365