Tyrosine kinase-stimulated guanine nucleotide exchange activity of Vav in T cell activation.
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.
Gulbins
E
E
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, CA 92037.
Coggeshall
K M
KM
Baier
G
G
Katzav
S
S
Burn
P
P
Altman
A
A
D016227:Benzoquinones; D018797:Cell Cycle Proteins; D005656:Fungal Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006801:Humans; D047029:Lactams, Macrocyclic; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D016853:Muromonab-CD3 / Q000494:pharmacology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D011809:Quinones / Q000494:pharmacology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020668:rap GTP-Binding Proteins
D016227:Benzoquinones; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D047029:Lactams, Macrocyclic; C000715470:MAS1 protein, human; D016853:Muromonab-CD3; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011809:Quinones; D017260:Receptor-CD3 Complex, Antigen, T-Cell; C496618:VAV1 protein, human; D006153:Guanosine Diphosphate; D017828:Rifabutin; C020754:herbimycin; D006160:Guanosine Triphosphate; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019204:GTP-Binding Proteins; D020668:rap GTP-Binding Proteins