Phospholipase D-mediated hydrolysis of phosphatidylcholine: role in cell signalling.

Journal of lipid mediators Pub Date : 1993-11-01
M Liscovitch, P Ben-Av, M Danin, G Faiman, H Eldar, E Livneh
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Abstract

Studies carried out in many laboratories have demonstrated the activation of phospholipase D (PLD) by a variety of receptor agonists and in many cell types. The signal-dependent formation of phosphatidic acid (PA), by PLD-catalyzed hydrolysis of phosphatidylcholine (PC), may represent a novel and ubiquitous signal transduction pathway in mammalian cells. The mode(s) of coupling between agonist receptors and PLD activation are not well understood. Studies utilizing NIH-3T3 fibroblasts indicated that PLD activation by different mitogens involves distinct mechanisms. Protein kinase C (PKC) seems to play a role both as a mediator and as a modulator of PLD activation. The role of PKC was further examined in Swiss/3T3-derived fibroblasts which stably overexpress PKC-alpha. In these cells, both basal and agonist-stimulated PLD activity are higher than in control cells. In vitro analysis of PLD activity in detergent-solubilized cell membranes, utilizing exogenous C6-NBD-PC as fluorescent substrate, showed nearly 2-fold higher activity in membranes from cells that overexpress PKC-alpha. These results suggest that PKC-alpha may play a role in regulating PLD expression. The PLD product PA was identified as a precursor of 'late phase' diacylglycerol which, at least in some cases, was temporally correlated and causally related to the sustained activation of PKC. However, PA may itself act as an intracellular messenger in its own right, although immediate targets for its action have not yet been identified. Activation of phosphoinositide-phospholipase C, PLD and phospholipase A2 seems to comprise a signaling cascade which is typically utilized by most (if not all) Ca(2+)-mobilizing agonists.

磷脂酶d介导的磷脂酰胆碱水解:在细胞信号传导中的作用。
在许多实验室进行的研究表明,磷脂酶D (PLD)被多种受体激动剂和许多细胞类型激活。磷脂酸(PA)是由pld催化的磷脂酰胆碱(PC)水解而形成的,这可能是哺乳动物细胞中一种新的、普遍存在的信号转导途径。激动剂受体与PLD激活之间的耦合模式尚不清楚。利用NIH-3T3成纤维细胞的研究表明,PLD被不同的有丝分裂原激活涉及不同的机制。蛋白激酶C (PKC)似乎既是PLD激活的中介又是调节性的。我们进一步研究了PKC在瑞士/ 3t3衍生成纤维细胞中的作用,这些成纤维细胞稳定过表达PKC- α。在这些细胞中,基础和激动剂刺激的PLD活性都高于对照细胞。利用外源C6-NBD-PC作为荧光底物,体外分析了洗涤剂溶解细胞膜上PLD的活性,结果显示,过表达pkc - α的细胞的细胞膜上PLD的活性高出近2倍。这些结果表明pkc - α可能在调节PLD表达中发挥作用。PLD产物PA被确定为“晚期”二酰基甘油的前体,至少在某些情况下,与PKC的持续激活具有时间相关性和因果关系。然而,PA本身可能作为细胞内信使,尽管其作用的直接目标尚未确定。磷酸肌醇-磷脂酶C、PLD和磷脂酶A2的激活似乎包括一个信号级联,通常被大多数(如果不是全部)Ca(2+)动员激动剂利用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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