Mitogenic effects of pertussis toxin-sensitive G-protein α subunits: The mitogenic action of α_i2 in NIH 3T3 cells is mimicked by α_i1, but not α_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 α_i2 subunit have been shown to induce partial transformation in fibroblasts. In order to determine whether other PTX-sensitive G-protein scan stimulate mitogenic pathways, we stably expressed constitutively activated G-protein α_i1 and α_i3 subunits in NIH 3T3 cells. Expression of activated α_i1, α_i2 or α_i3 results in inhibition of forskolin-stimulated cAMP accumulation in intact cells. Constitutively activated α_i1, but not α_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 α_i1 and α_i2 are both capable of transducing mitogenic signals, but that α_i3 is not involved in the regulation of fibroblast growth. Furthermore, adenylyl cyclase inhibition is clearly not sufficient to explain the effect of α_i2 on fibroblast growth.