Oude Weernink Paschal A, López de Jesús Maider, Schmidt Martina
Institut für Pharmakologie, Universitätsklinikum Essen, Essen, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2007 Feb;374(5-6):399-411. doi: 10.1007/s00210-007-0131-4. Epub 2007 Jan 24.
Hydrolysis of phosphatidylcholine by phospholipase D (PLD) leads to the generation of the versatile lipid second messenger, phosphatidic acid (PA), which is involved in fundamental cellular processes, including membrane trafficking, actin cytoskeleton remodeling, cell proliferation and cell survival. PLD activity can be dramatically stimulated by a large number of cell surface receptors and is elaborately regulated by intracellular factors, including protein kinase C isoforms, small GTPases of the ARF, Rho and Ras families and, particularly, by the phosphoinositide, phosphatidylinositol 4,5-bisphosphate (PIP(2)). PIP(2) is well known as substrate for the generation of second messengers by phospholipase C, but is now also understood to recruit and/or activate a variety of actin regulatory proteins, ion channels and other signaling proteins, including PLD, by direct interaction. The synthesis of PIP(2) by phosphoinositide 5-kinase (PIP5K) isoforms is tightly regulated by small GTPases and, interestingly, by PA as well, and the concerted formation of PIP(2) and PA has been shown to mediate receptor-regulated cellular events. This review highlights the regulation of PLD by membrane receptors, and describes how the close encounter of PLD and PIP5K isoforms with small GTPases permits the execution of specific cellular functions.
磷脂酶D（PLD）催化磷脂酰胆碱水解，生成多功能脂质第二信使磷脂酸（PA），PA参与包括膜运输、肌动蛋白细胞骨架重塑、细胞增殖和细胞存活等在内的基本细胞过程。大量细胞表面受体可显著刺激PLD活性，细胞内因子，包括蛋白激酶C亚型、ARF、Rho和Ras家族的小GTP酶，特别是磷酸肌醇磷脂酰肌醇4,5 - 二磷酸（PIP(2)），对其进行精细调控。PIP(2)作为磷脂酶C生成第二信使的底物广为人知，但现在也被认为可通过直接相互作用募集和/或激活多种肌动蛋白调节蛋白、离子通道和其他信号蛋白，包括PLD。磷酸肌醇5 - 激酶（PIP5K）亚型合成PIP(2)的过程受到小GTP酶以及有趣的是还受到PA的严格调控，并且已证明PIP(2)和PA的协同形成介导受体调节的细胞事件。本综述重点介绍了膜受体对PLD的调控，并描述了PLD和PIP5K亚型与小GTP酶的紧密相互作用如何实现特定细胞功能的执行。
