Suppression of Ras-induced transformation of NIH 3T3 cells by activated G alpha s.
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.
Chen
J
J
Department of Biochemistry, Mount Sinai School of Medicine, City University of New York, NY 10029.
Iyengar
R
R
D016475:3T3 Cells; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D011905:Genes, ras; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D016297:Mutagenesis, Site-Directed; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D019204:GTP-Binding Proteins