Abstract
The vav proto-oncogene product (Vav) is expressed exclusively in hematopoietic cells and is reported to have guanine nucleotide exchange activity. Here we report that granulocyte-macrophage colony-stimulating factor, interleukin-3, and erythropoietin induce tyrosine phosphorylation of Vav in a human leukemia cell line UT-7. Tyrosine phosphorylation of Vav is rapid and transient; it occurs within 1 min of the stimulation and at physiological concentrations of the factors. Furthermore, we show that Vav is constitutively associated with the adapter molecule Grb2/Ash in UT-7. These data suggest that tyrosine kinases, the adapter Grb2/Ash, and the guanine nucleotide exchange factor Vav are members of a signaling pathway leading to Ras activation in hematopoietic cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Cell Cycle Proteins*
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ErbB Receptors / metabolism
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Erythropoietin / pharmacology
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GRB2 Adaptor Protein
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Humans
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Interleukin-3 / pharmacology
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Leukemia / genetics
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Leukemia / metabolism*
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Molecular Sequence Data
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Neoplasm Proteins / metabolism*
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Phosphorylation / drug effects
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Protein-Tyrosine Kinases / metabolism*
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Proteins / 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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Proto-Oncogene Proteins pp60(c-src) / metabolism
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Signal Transduction / physiology
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Stimulation, Chemical
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Tumor Cells, Cultured
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ras Proteins / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Cell Cycle Proteins
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GRB2 Adaptor Protein
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GRB2 protein, human
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Interleukin-3
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MAS1 protein, human
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Neoplasm Proteins
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Proteins
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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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VAV1 protein, human
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Erythropoietin
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Granulocyte-Macrophage Colony-Stimulating Factor
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ErbB Receptors
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Protein-Tyrosine Kinases
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Proto-Oncogene Proteins pp60(c-src)
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ras Proteins