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.