Abstract
Phosphoinositide-specific phospholipase C (PI-PLC) catalyzes the hydrolysis of phosphatidylinositol 4, 5-bisphosphate to inositol 1, 4, 5-trisphosphate (IP3) and diacylglycerol. IP3 induces the release of Ca2+ from intracellular stores, and diacylglycerol acts as the physiological activator of protein kinase C. Several distinct PI-PLC enzymes have been identified from various cells. Based on the primary sequences, PI-PLC isozymes are divided into three families: PLC-β, PLC-γ, and PLC-δ. Substantial evidence has strongly suggested that G proteins regulate PI-PLC in various cell-stimulation systems and that there might be two distinct pathways (pertussis toxin-sensitive and pertussis toxin-insensitive). Recently, it has become apparent that β-type PLC isoforms are activated by the heterotrimeric G protein subfamily Gq. Careful studies using in vitro and in vivo reconstitution systems have further suggested that the α-subunits of Gq/11/16 specifically regulate PLC-β1 and PLC-β3 and that the βγ-subunits of the Gi subfamily interact with PLC-β2, which are considered to be responsible for the pertussis toxin-insensitive and the pertussis toxin-sensitive pathways, respectively. In this paper, involvement of G proteins in the regulation of phospholipase A2 and phosphatidylcholine-specific PLC and PLD is also discussed.
