Suppression of ras-induced transformation of NIH 3T3 cells by activated Gα_s

Conversion of external signals into proliferative responses may be mediated by interactions between signaling pathways that control cell proliferation. Interactions between Gα_s, the α 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 Gα_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 Gα_s and 8-Br-cAMP suppressed H-Ras-induced transformation of NIH 3T3 cells. Apparently, Gα_s inhibits proliferative signals from Ras by stimulating cAMP production and activating protein kinase A.