Regulation and cellular roles of phosphoinositide 5-kinases

The membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2), plays a critical role in various, apparently very different cellular processes. As precursor for second messengers generated by phospholipase C isoforms and class I phosphoinositide 3-kinases, PIP2 is indispensable for cellular signaling by membrane receptors. In addition, PIP2 directly affects the localization and activity of many cellular proteins via specific interaction with unique phosphoinositide-binding domains and thereby regulates actin cyloskeletal dynamics, vesicle trafficking, ion channel activity, gene expression and cell survival. The activity and subcellular localization of phosphatidylinositol 4-phosphate 5-kinase (PIP5K) isoforms, which catalyze the formation of PIP2, are actively regulated by membrane receptors, by phosphorylation and by small GTPases of the Rho and ARF families. Spatially and temporally organized regulation of PIP2 synthesis by PIP5K enables dynamic and versatile PIP2 signaling and represents an important link in the execution of cellular tasks by Rho and ARF GTPases. (C) 2004 Elsevier B.V. All rights reserved.