Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE

Abstract

Phospholipase Cgamma1 (PLC-gamma1) hydrolyses phosphatidylinositol-4,5-bisphosphate to the second messengers inositol-1,4,5-trisphosphate and diacylglycerol. PLC-gamma1 also has mitogenic activity upon growth-factor-dependent tyrosine phophorylation(1,2); however, this activity is not dependent on the phospholipase activity of PLC-gamma1, but requires an SH3 domain(3,4). Here, we demonstrate that PLC-gamma1 acts as a guanine nucleotide exchange factor (GEF) for PIKE (phosphatidylinositol-3-OH kinase (PI(3)K) enhancer). PIKE is a nuclear GTPase that activates nuclear PI(3)K activity, and mediates the physiological activation by nerve growth factor (NGF) of nuclear PI(3)K activity(5). This enzymatic activity accounts for the mitogenic properties of PLC-gamma1.