Ghosh Moumita, Tucker Dawn E, Burchett Scott A, Leslie Christina C
Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Prog Lipid Res. 2006 Nov;45(6):487-510. doi: 10.1016/j.plipres.2006.05.003. Epub 2006 Jun 15.
The Group IV phospholipase A2 family is comprised of six intracellular enzymes commonly called cytosolic phospholipase A2 (cPLA2) alpha, cPLA2beta, cPLA2gamma, cPLA2delta, cPLA2epsilon and cPLA2zeta. 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 PLA2s, Pseudomonas aeruginosa ExoU and NTE) contain the Ser/Asp catalytic dyad characteristic of Group IV PLA2s, and recent structural analysis of patatin has confirmed its structural similarity to cPLA2alpha. A characteristic of all these serine acylhydrolases is their ability to carry out multiple reactions to varying degrees (PLA2, PLA1, lysophospholipase and transacylase activities). cPLA2alpha, the most extensively studied Group IV PLA2, is widely expressed in mammalian cells and mediates the production of functionally diverse lipid products in response to extracellular stimuli. It has PLA2 and lysophospholipase activities and is the only PLA2 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, cPLA2alpha 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 PLA2s suggests they may have distinct mechanisms of regulation and functional roles.
IV族磷脂酶A2家族由六种细胞内酶组成，通常称为胞质磷脂酶A2（cPLA2）α、cPLA2β、cPLA2γ、cPLA2δ、cPLA2ε和cPLA2ζ。它们与丝状真菌的磷脂酶A和磷脂酶B/溶血磷脂酶最为同源，特别是在含有参与催化的保守残基的区域。然而，许多其他丝氨酸酰基水解酶（马铃薯Patatin、VI族PLA2、铜绿假单胞菌ExoU和NTE）含有IV族PLA2特有的Ser/Asp催化二元组，最近对马铃薯Patatin的结构分析证实了它与cPLA2α的结构相似性。所有这些丝氨酸酰基水解酶的一个特点是它们能够不同程度地进行多种反应（PLA2、PLA1、溶血磷脂酶和转酰基酶活性）。cPLA2α是研究最广泛的IV族PLA2，在哺乳动物细胞中广泛表达，并介导功能多样的脂质产物的产生以响应细胞外刺激。它具有PLA2和溶血磷脂酶活性，是唯一对含有花生四烯酸的磷脂底物具有特异性的PLA2。由于其在启动激动剂诱导的花生四烯酸释放以产生类二十烷酸中的作用，cPLA2α的激活在调节各种组织的正常和病理过程中很重要。目前关于其他IV族PLA2的生化特性和组织分布的信息表明它们可能具有不同的调节机制和功能作用。
