Tyrosine phosphorylation and activation of pp60^c-src and pp125^FAK in bradykinin-stimulated fibroblasts

Bradykinin (BK) stimulates protein tyrosine phosphorylation in human foreskin fibroblasts (K.-M. Lee, K. Toscas, and M. L. Villereal. J. Biol. Chem. 268: 9945-9948, 1993). The major tyrosine phosphorylation occurs in proteins of a molecular mass of 130 and 70 kDa. In this report, we demonstrate that focal adhesionassociated tyrosine kinase, pp125^FAK, is one component of the 130-kDa phosphotyrosine band. The BK-stimulated pp125^FAK tyrosine phosphorylation level is well correlated with increased kinase activity, as assessed by in vitro immune complex kinase assays. We have identified paxillin, a protein that is localized in focal adhesions, as a component of the 70-kDa phosphotyrosine band. In addition to identifying the two proteins responsible for the major phosphotyrosine bands, we also report that pp60^c-src is tyrosine phosphorylated and activated in response to BK, as analyzed by immunoblotting and in vitro kinase assays, respectively. These findings indicate, for the first time, that the BK receptor is coupled to the important protooncogene c-src and that the src pathway may mediate some of the events downstream from BK binding.