Phospholipase A2

Phospholipase A(2) (PLA(2)) catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid (AA), a precursor of eicosanoids including prostaglandins (PGs) and leukotrienes (LTs). The same reaction also produces lysophosholipids, which represent another class of lipid mediators. So far, at least 19 enzymes that possess PLA(2) activity have been identified in mammals. The secretory PLA(2) (sPLA(2)) family, in which 10 isozymes have been identified, consists of low-molecular-weight, Ca2+-requiring, secretory enzymes that have been implicated in a number of biological processes, such as modification of eicosanoid generation, inflammation, host defense, and atherosclerosis. The cytosolic PLA(2) (cPLA(2)) family consists of 3 enzymes, among which cPLA(2)alpha plays an essential role in the initiation of AA metabolism. Intracellular activation of cPLA(2)alpha is tightly regulated by Ca2+ and phosphorylation. The Ca2+-independent PLA(2) (iPLA(2)) family contains 2 enzymes and may play a major role in membrane phospholipid remodeling. The platelet-activating factor (PAF) acetylhydrolase (PAF-AH) family represents a unique group of PLA(2) that contains 4 enzymes exhibiting unusual substrate specificity toward PAF and/or oxidized phospholipids. In this review, we will overview current understanding of the properties and functions of each enzyme belonging to the sPLA(2), cPLA(2), and iPLA(2) families, which have been implicated in signal transduction.