Thematic Review Series: Phospholipases: Central Role in Lipid Signaling and Disease Cytosolic phospholipase A2 : physiological function and role in disease

The group IV phospholipase A(2) (PLA(2)) family is comprised of six intracellular enzymes (GIVA, -B, -C, -D, -E, and -F) commonly referred to as cytosolic PLA(2) (cPLA(2)) alpha, -beta, -gamma, -delta, -epsilon, and -zeta. They contain a Ser-Asp catalytic dyad and all except cPLA(2)gamma have a C2 domain, but differences in their catalytic activities and subcellular localization suggest unique regulation and function. With the exception of cPLA(2)alpha, the focus of this review, little is known about the in vivo function of group IV enzymes. cPLA(2)alpha catalyzes the hydrolysis of phospholipids to arachidonic acid and lysophospholipids that are precursors of numerous bioactive lipids. The regulation of cPLA(2)alpha is complex, involving transcriptional and posttranslational processes, particularly increases in calcium and phosphorylation. cPLA(2)alpha is a highly conserved widely expressed enzyme that promotes lipid mediator production in human and rodent cells from a variety of tissues. The diverse bioactive lipids produced as a result of cPLA(2)alpha activation regulate normal physiological processes and disease pathogenesis in many organ systems, as shown using cPLA(2)alpha KO mice.Jlr However, humans recently identified with cPLA(2)alpha deficiency exhibit more pronounced effects on health than observed in mice lacking cPLA(2)alpha, indicating that much remains to be learned about this interesting enzyme.