Mitogenic effects of pertussis toxin-sensitive G-protein alpha subunits: the mitogenic action of alpha i2 in NIH 3T3 cells is mimicked by alpha i1, but not alpha i3.

In fibroblasts and other cell types, pertussis toxin (PTX) inhibits DNA synthesis in response to serum and certain growth factors. GTPase deficient forms of the PTX-sensitive G-protein alpha i2 subunit have been shown to induce partial transformation in fibroblasts. In order to determine whether other PTX-sensitive G-proteins can stimulate mitogenic pathways, we stably expressed constitutively activated G-protein alpha i1 and alpha i3 subunits in NIH 3T3 cells. Expression of activated alpha i1, alpha i2 or alpha i3 results in inhibition of forskolin-stimulated cAMP accumulation in intact cells. Constitutively activated alpha i1, but not alpha i3, induces a loss of contact inhibition, a loss of anchorage-dependence, a reduced serum requirement and a decreased doubling time in NIH 3T3 cells. We conclude that alpha i1 and alpha i2 are both capable of transducing mitogenic signals, but that alpha i3 is not involved in the regulation of fibroblast growth. Furthermore, adenylyl cyclase inhibition is clearly not sufficient to explain the effect of alpha i2 on fibroblast growth.