Signal transduction by beta 1 integrin receptors in human chondrocytes in vitro: collaboration with the insulin-like growth factor-1 receptor

We have examined the mechanism by which collagen-binding integrins co-opera te with insulin-like growth factor-I (IGF-I) receptors (IGF-IR) to regulate chondrocyte phenotype and differentiation. Adhesion of chondrocytes to ant i-beta 1 integrin antibodies or collagen type II leads to phosphorylation o f cytoskeletal and signalling proteins localized at focal adhesions, includ ing alpha-actinin, vinculin, paxillin and focal adhesion kinase (FAK). Thes e stimulate docking proteins such as Shc (Src-homology collagen). Moreover, exposure of collagen type II-cultured chondrocytes to IGF-I leads to co-im munoprecipitation of Shc protein with the TGF-IR and with beta 1, alpha 1 a nd alpha 5 integrins, but not with alpha 3 integrin. Shc then associates wi th growth factor receptor-bound protein 2 (Grb2), an adaptor protein and ex tracellular signal-regulated kinase. The expression of the docking protein Shc occurs only when chondrocytes are bound to collagen type II or integrin antibodies and increases when IGF-I is added, suggesting a collaboration b etween integrins and growth factors in a common/shared biochemical signalli ng pathway. Furthermore, these results indicate that focal adhesion assembl y may facilitate signalling via Shc, a potential common target for signal i ntegration between integrin and growth-factor signalling regulatory pathway s. Thus, the collagen-binding integrins and IGF-IR co-operate to regulate f ocal adhesion components and these signalling pathways have common targets (Shc-Grb2 complex) in subcellular compartments, thereby linking to the Rasm itogen-activated protein kinase signalling pathway. These events may play a role during chondrocyte differentiation.