REQUIREMENT FOR PHOSPHATIDYLINOSITOL TRANSFER PROTEIN IN EPIDERMAL GROWTH-FACTOR SIGNALING

Stimulation of phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis is a widespread mechanism for receptor-mediated signaling in eukaryot es. Cytosolic phosphatidylinositol transfer protein (PITP) is necessar y for guanosine triphosphate (GTP)-dependent hydrolysis of PIP2 by pho spholipase C-beta (PLC-beta), but the role of PITP is unclear. Stimula tion of phospholipase C-gamma (PLC-gamma) in A431 human epidermoid car cinoma cells treated with epidermal growth factor (EGF) required PITP. Stimulation of PI-4 kinase in cells treated with EGF also required PI TP. Coprecipitation studies revealed an EGF-dependent association of P ITP with the EGF receptor, with PI-4 kinase, and with PLC-gamma.