REGULATORY FUNCTIONS OF PHOSPHOLIPASE A(2)

Phospholipase A(2) (PLA(2)) plays crucial roles in diverse cellular re sponses, including phospholipid digestion and metabolism, host defense and signal transduction. PLA(2) provides precursors for generation of eicosanoids, such as prostaglandins (PGs) and leukotrienes (LTs), whe n the cleaved fatty acid is arachidonic acid, platelet-activating fact or (PAF) when the sn-1 position of the phosphatidylcholine contains an alkyl ether linkage and some bioactive lysophospholipids, such as lys ophosphatidic acid (lysoPA). As overproduction of these lipid mediator s causes inflammation and tissue disorders, it is extremely important to understand the mechanisms regulating the expression and functions o f PLA(2). Recent advances in molecular and cellular biology have enabl ed us to understand the molecular nature, possible function, and regul ation of a variety of PLA(2) isozymes. Mammalian tissues and cells gen erally contain more than one enzyme, each of which is regulated indepe ndently and exerts distinct functions. Here we classify mammalian PLA( 2)s into three large groups, namely, secretory (sPLA(2)), cytosolic (c PLA(2)), and Ca2+-independent PLA(2)s, on the basis of their enzymatic properties and structures and focus on the general undestanding of th e possible regulatory functions of each PLA(2) isozyme. In particular, the roles of type II sPLA(2) and cPLA(2) in lipid mediator generation are discussed.