SIGNIFICANCE OF PIP2 HYDROLYSIS AND REGULATION OF PHOSPHOLIPASE-C ISOZYMES

Phosphatidylinositol 4,5-bisphosphate (PIP2) is an important component of several intracellular signaling pathways. It serves as a substrate for phospholipase C, which produces the second messengers inositol 1, 4,5-trisphosphate and diacylglycerol. It is also a substrate for a pho sphatidylinositol 3-kinase, and regulates the function of a number of actin-binding proteins. PIP2 has been shown recently to serve as a cof actor for a phosphatidylcholine-specific phospholipase D and as a memb rane-attachment site for many signaling proteins containing pleckstrin homology domains. The need to stringently regulate the cellular conce ntration of PIP2 is reflected in part by the fact that there are at le ast ten distinct mammalian phospholipase C isozymes and multiple mecha nisms linking these isozymes to various receptors.