TYROSINE PHOSPHORYLATION AND ACTIVATION OF VAV GTP GDP EXCHANGE ACTIVITY IN ANTIGEN RECEPTOR-TRIGGERED B-CELLS/

Ag receptor triggering in B cells stimulates the activity of receptor- associated tyrosine protein kinases (TPK), leading to tyrosine phospho rylation of several cellular substrates, one of which is the Vav proto -oncogene product. We have recently determined that Vav is a TPK-regul ated guanine nucleotide exchange factor for Ras in T cells. Here, we s how that B cell extracts or Vav immunoprecipitates contain a Ras GDP/C TP exchange activity that is stimulated upon surface Ig (sIg) triggeri ng. The receptor-mediated stimulation of Vav exchange activity was blo cked by the TPK antagonist, herbimycin A. Furthermore, immunodepletion of Vav from the B cell extracts removed similar to 80% of the Ras GDP /GTP exchange activity. These findings indicate, first, that B cell-de rived Vav possesses GDP/CTP exchange activity for Ras; second, that th e exchange activity of Vav is accelerated by a sig-triggered, herbimyc in A-sensitive TPK and, third, that Vav accounts for most of the recep tor-stimulated Ras GDP/GTP exchange activity. Thus, Vav may serve as a critical component in sIg-mediated signal transduction pathways by co upling receptor-associated TPK to the activation of Ras proteins.