Abstract
Conversion of external signals into proliferative responses may be mediated by interactions between signaling pathways that control cell proliferation. Interactions between G alpha s, the alpha subunit of the heterotrimeric guanine nucleotide binding protein that stimulates adenylyl cyclase, and Ras, an important element in growth factor signaling, were studied. Expression of activated G alpha s in NIH 3T3 cells increased intracellular concentrations of adenosine 3',5'-monophosphate (cAMP) and inhibited H-Ras-stimulated DNA synthesis and mitogen-activated protein kinase activity. Activated G alpha s and 8-Br-cAMP suppressed H-Ras-induced transformation of NIH 3T3 cells. Apparently, G alpha s inhibits proliferative signals from Ras by stimulating cAMP production and activating protein kinase A.
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.
MeSH terms
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3T3 Cells
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8-Bromo Cyclic Adenosine Monophosphate / pharmacology
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Animals
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Cell Division
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Cell Line
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Cell Transformation, Neoplastic*
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Cyclic AMP / metabolism
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Enzyme Activation
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / physiology*
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Genes, ras*
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Mice
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Mitogen-Activated Protein Kinase 1
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Mutagenesis, Site-Directed
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / metabolism
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / metabolism
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Signal Transduction
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Transfection
Substances
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8-Bromo Cyclic Adenosine Monophosphate
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Cyclic AMP
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Cyclic AMP-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1
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GTP-Binding Proteins