Abstract
The protooncogene ras acts as a component of signal-transduction networks in many kinds of cells. The ras gene product (p21) is a GTP-binding protein, and the activity of the protein is regulated by bound GDP/GTP. Recent studies have shown that a certain class of growth factors stimulates the formation of active p21-GTP complexes in fibroblasts and that oncogene products with enhanced tyrosine kinase activities have a similar effect on ras p21. We have measured the ratio of active GTP-bound p21 to total p21 in several lymphoid and myeloid cell lines in order to understand the role of ras in the proliferation of these cells. Interleukin 2 (IL-2), IL-3, and granulocyte/macrophage colony-stimulating factor (GM-CSF) enhance the formation of the active p21.GTP, whereas IL-4 has no effect on p21-bound GDP/GTP. These results strongly suggest that ras p21 acts as a transducer of signals from IL-2, IL-3, and GM-CSF, but not from IL-4.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / physiology
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Cell Line
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Epidermal Growth Factor / pharmacology
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Granulocyte-Macrophage Colony-Stimulating Factor / physiology*
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Guanosine Diphosphate / metabolism
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Guanosine Triphosphate / metabolism
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In Vitro Techniques
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Interleukins / physiology*
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Ionomycin / pharmacology
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Lymphocytes / physiology*
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Mice
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Protein Kinase C / physiology
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Proto-Oncogene Proteins p21(ras) / physiology*
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / physiology*
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Receptors, Interleukin-2 / physiology*
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Receptors, Interleukin-3 / physiology*
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Receptors, Interleukin-4
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Receptors, Mitogen / physiology*
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Signal Transduction*
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Tetradecanoylphorbol Acetate / pharmacology
Substances
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Interleukins
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
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Receptors, Interleukin-2
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Receptors, Interleukin-3
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Receptors, Interleukin-4
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Receptors, Mitogen
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Guanosine Diphosphate
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Ionomycin
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Epidermal Growth Factor
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Granulocyte-Macrophage Colony-Stimulating Factor
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Guanosine Triphosphate
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Protein Kinase C
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Proto-Oncogene Proteins p21(ras)
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Tetradecanoylphorbol Acetate
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Calcium