LCK REGULATES VAV ACTIVATION OF MEMBERS OF THE RHO-FAMILY OF GTPASE

Vav is a member of a family of oncogene proteins that share an approxi mately 250-amino-acid motif called a Dbl homology domain, Paradoxicall y, Dbl itself and other proteins containing a Dbl domain catalyze GTP- GDP exchange for Rho family proteins, whereas Vav has been reported to catalyze GTP-GDP exchange for Ras proteins. We present Saccharomyces cerevisiae genetic data, in vitro biochemical data, and animal cell bi ological data indicating that Vav is a guanine nucleotide exchange fac tor for Rho-related proteins, but in similar genetic and biochemical e xperiments we fail to find evidence that Vav is a guanine nucleotide e xchange factor for Pas. Further, we present data indicating that the L ck kinase activates the guanine nucleotide exchange factor and transfo rming activity of Vav.