Abstract
Vav is a member of a family of oncogene proteins that share an approximately 250-amino-acid motif called a Dbl homology domain. Paradoxically, Dbl itself and other proteins containing a Dbl domain catalyze GTP-GDP exchange for Rho family proteins, whereas Vav has been reported to catalyze GTP-GDP exchange for Ras proteins. We present Saccharomyces cerevisiae genetic data, in vitro biochemical data, and animal cell biological data indicating that Vav is a guanine nucleotide exchange factor for Rho-related proteins, but in similar genetic and biochemical experiments we fail to find evidence that Vav is a guanine nucleotide exchange factor for Ras. Further, we present data indicating that the Lck kinase activates the guanine nucleotide exchange factor and transforming activity of Vav.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cell Line
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Fibroblasts
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GTP-Binding Proteins / metabolism*
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Guanine Nucleotide Exchange Factors*
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Guanosine Diphosphate / metabolism
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Humans
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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Phosphorylation
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-vav
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Pseudopodia
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Rats
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Recombinant Fusion Proteins / metabolism
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Saccharomyces cerevisiae / physiology
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Saccharomyces cerevisiae Proteins*
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Signal Transduction / physiology*
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Suppression, Genetic
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cdc42 GTP-Binding Protein
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rac GTP-Binding Proteins
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ras Proteins / metabolism
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rhoA GTP-Binding Protein
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src-Family Kinases / metabolism*
Substances
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CDC24 protein, S cerevisiae
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Cell Cycle Proteins
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Guanine Nucleotide Exchange Factors
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MCF2 protein, human
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-vav
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Recombinant Fusion Proteins
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Saccharomyces cerevisiae Proteins
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VAV1 protein, human
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Vav1 protein, rat
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Guanosine Diphosphate
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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src-Family Kinases
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GTP-Binding Proteins
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cdc42 GTP-Binding Protein
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rac GTP-Binding Proteins
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ras Proteins
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rhoA GTP-Binding Protein