Tyrosine kinase-stimulated guanine nucleotide exchange activity of Vav in T cell activation

Science. 1993 May 7;260(5109):822-5. doi: 10.1126/science.8484124.

Abstract

The hematopoietically expressed product of the vav proto-oncogene, Vav, shared homology with guanine nucleotide releasing factors (GRFs) [also called guanosine diphosphate-dissociation stimulators (GDSs)] that activate Ras-related small guanosine triphosphate (GTP)-binding proteins. Human T cell lysates or Vav immunoprecipitates possessed GRF activity that increased after T cell antigen receptor (TCR)-CD3 triggering; an in vitro-translated Vav fragment that contained the putative GRF domain was also active. Vav-associated GRF stimulation after TCR-CD3 ligation paralleled its tyrosine phosphorylation; both were blocked by a protein tyrosine kinase (PTK) inhibitor. Vav also was a substrate for the p56lck PTK. Thus, Vav is a PTK-regulated GRF that may be important in TCR-CD3-initiated signal transduction through the activation of Ras.

Publication types

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

MeSH terms

  • Benzoquinones
  • Cell Cycle Proteins*
  • Fungal Proteins / metabolism
  • GTP-Binding Proteins / metabolism
  • Guanosine Diphosphate / metabolism*
  • Guanosine Triphosphate / metabolism*
  • Humans
  • Lactams, Macrocyclic
  • Lymphocyte Activation
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Muromonab-CD3 / pharmacology
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-vav
  • Quinones / pharmacology
  • Receptor-CD3 Complex, Antigen, T-Cell / immunology
  • Rifabutin / analogs & derivatives
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tumor Cells, Cultured
  • rap GTP-Binding Proteins

Substances

  • Benzoquinones
  • Cell Cycle Proteins
  • Fungal Proteins
  • Lactams, Macrocyclic
  • Muromonab-CD3
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-vav
  • Quinones
  • Receptor-CD3 Complex, Antigen, T-Cell
  • VAV1 protein, human
  • Guanosine Diphosphate
  • Rifabutin
  • herbimycin
  • Guanosine Triphosphate
  • Protein-Tyrosine Kinases
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • GTP-Binding Proteins
  • rap GTP-Binding Proteins