Beta4 integrin activates a Shp2-Src signaling pathway that sustains HGF-induced anchorage-independent growth.

ABSTRACT: Despite being a cell-matrix adhesion molecule, beta4 integrin can prompt the multiplication of neoplastic cells dislodged from their substrates (anchorage-independent growth). However, the molecular events underlying this atypical behavior remain partly unexplored. We found that activation of the Met receptor for hepatocyte growth factor results in the tyrosine phosphorylation of beta4, which is instrumental for integrin-mediated recruitment of the tyrosine phosphatase Shp2. Shp2 binding to beta4 enhances the activation of Src, which, in turn, phosphorylates the multiadaptor Gab1 predominantly on consensus sites for Grb2 association, leading to privileged stimulation of the Ras-extracellular signal-regulated kinase (ERK) cascade. This signaling axis can be inhibited by small interfering RN

SUBMITTER: Bertotti A 

PROVIDER: S-EPMC2064708 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature