THE ADAPTER PROTEIN SHC COUPLES A CLASS OF INTEGRINS TO THE CONTROL OF CELL-CYCLE PROGRESSION

We provide evidence that a class of integrins combines with the adapto r She and thereby with Grb2. Coimmunoprecipitation and mutagenesis exp eriments indicate that the recruitment of She is specified by the extr acellular or transmembrane domain of integrin cu subunit and suggest t hat this process is mediated by caveolin. Mutagenesis and dominant-neg ative inhibition studies reveal that She is necessary and sufficient f or activation of the MAP kinase pathway in response to integrin ligati on. Mitogens and She-activating integrins cooperate to promote transcr iption from the Fos serum response element and transit through G1. In contrast, adhesion mediated by integrins not linked to She results in cell cycle arrest and apoptosis even in presence of mitogens. These fi ndings indicate that the association of specific integrins with She re gulates cell survival and cell cycle progression.