AN ESSENTIAL ROLE FOR PHOSPHATIDYLINOSITOL TRANSFER PROTEIN IN PHOSPHOLIPASE C-MEDIATED INOSITOL LIPID SIGNALING

Transmembrane signaling by the phospholipase C-beta (PLC-beta) pathway is known to require at least three components: the receptor, the G pr otein, and the PLC. Recent studies have indicated that if the cytosol is allowed to leak out of HL60 cells, then G protein-stimulated PLC ac tivity is greatly diminished, indicating an essential role for a cytos olic component(s). We now report the complete purification of one comp onent based on its ability to reconstitute GTPgammaS-mediated PLC acti vity and identify it as the phosphatidylinositol transfer protein (PI- TP). Based on the in vitro effects of PI-TP, we surmise that it is inv olved in transporting PI from intracellular compartments for conversio n to PI bisphosphate (PIP2) prior to hydrolysis by PLC-beta2/PLC-beta3 , the endogenous PLC isoforms present in these cells.