4.6 Review

Properties of the Group IV phospholipase A2 family

Journal

PROGRESS IN LIPID RESEARCH
Volume 45, Issue 6, Pages 487-510

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.plipres.2006.05.003

Keywords

phospholipase A2; C2 domain; calcium; eicosanoids; arachidonic acid; catalytic dyad

Funding

  1. NHLBI NIH HHS [HL34303, HL77064, HL61378] Funding Source: Medline

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The Group IV phospholipase A(2) family is comprised of six intracellular enzymes commonly called cytosolic phospholipase A(2) (cPLA(2)) alpha, cPLA(2)beta, cPLA(2)gamma, cPLA(2)delta, cPLA(2)epsilon, and cPLA(2)xi. They are most homologous to phospholipase A and phospholipase B/lysophospholipases of filamentous fungi particularly in regions containing conserved residues involved in catalysis. However, a number of other serine acylhydrolases (patatin, Group VI PLA(2)s, Pseudomonas aeruginosa ExoU and NTE) contain the Ser/Asp catalytic dyad characteristic of Group IV PLA(2)s, and recent structural analysis of patatin has confirmed its structural similarity to cPLA(2)alpha. A characteristic of all these serine acylhydrolases is their ability to carry out multiple reactions to varying degrees (PLA(2), PLA(1), lysophospholipase and transacylase activities). cPLA(2)alpha, the most extensively studied Group IV PLA(2), is widely expressed in mammalian cells and mediates the production of functionally diverse lipid products in response to extracellular stimuli. It has PLA(2) and lysophospholipase activities and is the only PLA(2) that has specificity for phospholipid substrates containing arachidonic acid. Because of its role in initiating agonist-induced release of arachidonic acid for the production of eicosanoids, cPLA(2)alpha activation is important in regulating normal and pathological processes in a variety of tissues. Current information available about the biochemical properties and tissue distribution of other Group IV PLA(2)s Suggests they may have distinct mechanisms of regulation and functional roles. (c) 2006 Elsevier Ltd. All rights reserved.

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