Integrin-dependent tyrosine phosphorylation and growth regulation by Vav

The proto-oncogene product p95Vav (Vav) undergoes rapid phosphorylation on tyrosine following stimulation of the T or B cell antigen receptor, and in response to a variety of other cell surface stimuli. Vav contains, among ot her, a guanine nucleotide exchange factor domain with homology to the Rho/R ac/CDC42 exchange protein Db1. It has been recently shown that Vav is funct ionally linked to small GTPases of the Rho family, suggesting that it is an activator of Rho GTPases and may participate in regulation of cytoskeletal organization. The present study shows that cell adhesion to fibronectin tr iggers rapid phosphorylation of Vav on tyrosine in Vav-transfected CHO cell s and in Jurkat T cells. Vav phosphorylation is strongly dependent on adhes ion and is mediated by beta 1 integrins. Furthermore, Vav overexpression en hances the adhesion-dependent increase in the rate and extent of phosphoryl ation on focal adhesion kinase and paxillin, and the formation of stress fi bers and lamellipodia, In addition, there is a marked increase in the amoun t of Vav localized to the triton-insoluble fraction following 1 h of incuba tion on FN. Finally, Vav increases the growth rate of the cells in an adhes ion-dependent manner. Our results strongly implicate Vav as a mediator of i ntegrin signal transduction.