The adaptor 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 adaptor She and thereby with Grb2. Coimmunoprecipitation and mutagenesis experiments indicate that the recruitment of She is specified by the extracellular or transmembrane domain of integrin cu subunit and suggest that this process is mediated by caveolin. Mutagenesis and dominant-negative inhibition studies reveal that She is necessary and sufficient for activation of the MAP kinase pathway in response to integrin ligation. Mitogens and She-activating integrins cooperate to promote transcription 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 findings indicate that the association of specific integrins with She regulates cell survival and cell cycle progression.