Tyrosine phosphorylation and activation of Vav GTP/GDP exchange activity in antigen receptor-triggered B cells

J Immunol. 1994 Mar 1;152(5):2123-9.


Ag receptor triggering in B cells stimulates the activity of receptor-associated tyrosine protein kinases (TPK), leading to tyrosine phosphorylation of several cellular substrates, one of which is the Vav proto-oncogene product. We have recently determined that Vav is a TPK-regulated guanine nucleotide exchange factor for Ras in T cells. Here, we show that B cell extracts or Vav immunoprecipitates contain a Ras GDP/GTP exchange activity that is stimulated upon surface Ig (slg) triggering. The receptor-mediated stimulation of Vav exchange activity was blocked by the TPK antagonist, herbimycin A. Furthermore, immunodepletion of Vav from the B cell extracts removed approximately 80% of the Ras GDP/GTP exchange activity. These findings indicate, first, that B cell-derived Vav possesses GDP/GTP exchange activity for Ras; second, that the exchange activity of Vav is accelerated by a slg-triggered, herbimycin A-sensitive TPK and, third, that Vav accounts for most of the receptor-stimulated Ras GDP/GTP exchange activity. Thus, Vav may serve as a critical component in slg-mediated signal transduction pathways by coupling receptor-associated TPK to the activation of Ras proteins.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Cell Cycle Proteins*
  • Cell Line
  • Guanine Nucleotide Exchange Factors
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • In Vitro Techniques
  • Mice
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-vav
  • Receptors, Antigen, T-Cell
  • Tyrosine / metabolism
  • ras Guanine Nucleotide Exchange Factors


  • Cell Cycle Proteins
  • Guanine Nucleotide Exchange Factors
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-vav
  • Receptors, Antigen, T-Cell
  • Vav1 protein, mouse
  • ras Guanine Nucleotide Exchange Factors
  • Guanosine Diphosphate
  • Tyrosine
  • Guanosine Triphosphate
  • Protein-Tyrosine Kinases