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Biological and Pharmaceutical Bulletin
Vol. 27 (2004) No. 8 P 1168-1173

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http://doi.org/10.1248/bpb.27.1168

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Cytosolic phospholipase A2α (cPLA2α) preferentially hydrolyzes phospholipids containing arachidonic acid and plays a key role in the biosynthesis of eicosanoids. This review discusses the essential features of cPLA2α regulation and addresses new insights into the functional properties of this enzyme. Full activation of the enzyme requires Ca2+ binding to an N-terminal C2 domain and phosphorylation on serine residues. Ca2+ binding induces translocation of cPLA2α from the cytosol to the perinuclear membranes. Serine phosphorylation is mediated by mitogen-activated protein kinases (MAPKs), Ca2+/calmodulin-dependent protein kinase II, and MAPK-interacting kinase Mnk1. Interaction with proteins and lipids, which include vimentin, annexins, NADPH oxidase, phosphatidylcholine, phosphatidylinositol 4,5-bisphosphate (PIP2), and ceramide-1-phosphate, can also modulate the activity of cPLA2α. Recent evidence has established the physiological and pathological roles of cPLA2α using cPLA2α knockout mice. This enzyme has been implicated in fertility, striated muscle growth, renal concentration, postischemic brain injury, arthritis, inflammatory bone resorption, intestinal polyposis, pulmonary fibrosis, acute respiratory distress syndrome, and autoimmune encephalomyelitis. Now novel three paralogs, cPLA2β, cPLA2γ, and cPLA2δ, have been identified in humans. cPLA2γ is distinct from others in that it is farnesylated and lacks the C2 domain. Biological roles for these new enzymes have not yet been defined.

Copyright © 2004 The Pharmaceutical Society of Japan

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