Suppression of G(iα2) enhances phospholipase C signalling

G-proteins mediate transmembrane signalling from a populous group of cell-surface receptors to a smaller group of effectors that includes adenylate cyclase, various ion channels and phospholipase C. Stem cells (F9 teratocarcinoma) or rat osteosarcoma 17/2.8 cells in which G(iα2) expression is abolished by antisense RNA display markedly elevated basal inositol 1,4,5-trisphosphate accumulation and a potentiated phospholipase C response to stimulatory hormones. Expression of the Q205L mutant of G(iα2), which is constitutively active, was found to block persistently hormonally stimulated phospholipase C activity, implicating G(iα2) as an inhibitory regulator of phospholipase C signalling. Analysis using G(iα2)-deficient adipocytes of transgenic mice provided further evidence for a role for G(iα2) in phospholipase C regulation, demonstrating in vivo that loss of G(iα2) elevates basal, and markedly potentiates hormonally stimulated, phospholipase C activity. This report demonstrates for the first time that a single G-protein, G(iα2), can regulate two distinct signalling pathways, i.e. adenylate cyclase and phospholipase C.