Identification of a novel cytosolic poly-phosphoinositide-specific phospholipase C (PLC-86) as the major G-protein-regulated enzyme.

Abstract

Activation of phosphoinositide -specific phospholipase C (PLC) generates two intracellular signals which play major roles in many cellular processes including secretion, proliferation and contraction. PLC activation by many receptors occurs via a guanine nucleotide regulatory protein, G(p). PLCs are found predominantly in the cytosolic fraction though some activity is membrane-associated. At least four families of isoenzymes of PLC (α, β, γ and δ) have been identified, but there is only scant evidence to indicate that any of the mammalian cytosolic activities are involved in G-protein-regulated signalling. In this study we demonstrate that the PLC activity from rat brain cytosol can be regulated in a G-protein-dependent manner in a reconstituted system using pre-permeabilized HL60 cells. We identify two enzymes, PLC-β and a novel 86 kDa enzyme (designated PLC-ε) as the G-protein-regulated enzymes. PLC-ε was found to be the major G-protein-regulated enzyme.