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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Comment
MeSH terms
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Benzoquinones
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Cell Cycle Proteins*
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Fungal Proteins / metabolism
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GTP-Binding Proteins / metabolism
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Guanosine Diphosphate / metabolism*
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Guanosine Triphosphate / metabolism*
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Humans
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Lactams, Macrocyclic
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Lymphocyte Activation
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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Muromonab-CD3 / pharmacology
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Phosphorylation
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Protein-Tyrosine Kinases / metabolism*
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Proto-Oncogene Mas
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-vav
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Quinones / pharmacology
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Receptor-CD3 Complex, Antigen, T-Cell / immunology
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Rifabutin / analogs & derivatives
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Signal Transduction
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Tumor Cells, Cultured
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rap GTP-Binding Proteins
Substances
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Benzoquinones
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Cell Cycle Proteins
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Fungal Proteins
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Lactams, Macrocyclic
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MAS1 protein, human
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Muromonab-CD3
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Proto-Oncogene Mas
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-vav
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Quinones
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Receptor-CD3 Complex, Antigen, T-Cell
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VAV1 protein, human
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Guanosine Diphosphate
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Rifabutin
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herbimycin
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Guanosine Triphosphate
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Protein-Tyrosine Kinases
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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GTP-Binding Proteins
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rap GTP-Binding Proteins