Phosphoinositides: Lipid Kinases and Phosphatases

Phosphoinositides (PIs) are a family of eight quantitatively minor membrane lipids playing important roles in the control of a variety of intracellular signaling mechanisms in eukaryotic cells (1 –4 ). The metabolism of these peculiar lipids is highly controlled by a set of enzymes such as kinases, phosphatases, and phospholipases. Phosphatidylinositol (PtdIns) is the quantitatively major PI and is sequentially phosphorylated by specific kinases to produce the different polyPIs that are biologically active compounds (1 ,2 ). The so-called canonical pathway involves 4- and 5-kinases and leads to the production of PtdIns(4,5)P₂ , which can be hydrolyzed by phospholi-pase C (PLC) generating diacylglycerol (DAG), an activator of protein kinase C (PKC), and inositol 1,4,5 tris -phosphate (InsP₃ ), stimulating calcium release from the endoplasmic reticulum (5 ). DAG can be degraded by lipases or, as in blood platelets, it can be rapidly phosphorylated by DAG-kinases to phosphatidic acid (PtdOH), a lipid that might have important biological roles (6 ).