Enhanced phospholipase C stimulation and transformation in NIH-3T3 cells expressing Q209LG_q-α-subunits

NIH-3T3 cells were transfected with cDNA encoding the native α-subunit of the G protein G_q(α_q) or a mutant (Q209L) form of α_q. Cells expressing Q209L-α_q showed greatly enhanced basal phospholipase C activity. Stimulation of phospholipase C activity by prostaglandin F_2α or fetal calf serum was increased up to 10-fold in Q209L-α_q-transfected cells. Continuous expression of Q209L-α_q or overexpression of α_q in NIH-3T3 cells resulted in formation of foci after 3 weeks. The number of foci was proportional to the number of transfected cells and was greater in cells expressing the Q209L-α_q than in cells that overexpressed the wild type α_q. Q209L-α_q-transfected NIH-3T3 cells also formed colonies in soft agar indicating their capacity to grow in an anchorage-independent manner. Expression of Q209L-α_q in Rat-1 cells resulted in enhanced basal and fetal calf serum-stimulated phospholipase C activity, but these cells were not transformed as assessed by either the focus formation or the soft agar colony formation assays. These results indicate that expression of continuously activated G_q-α can result in transformation in a cell type-specific manner.