Role of phospholipase d in g-protein coupled receptor function.
Role of phospholipase d in g-protein coupled receptor function.
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DOI：
10.3390/membranes4030302
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发表时间：
2014-07-03
期刊：
影响因子：
4.2
通讯作者：
Koch T
中科院分区：
文献类型：
--
作者：
Brandenburg LO;Pufe T;Koch T
许多G蛋白偶联受体的长时间激动剂暴露诱导受体快速磷酸化和从G蛋白解偶联。这些脱敏受体的再敏化需要内吞作用和随后的去磷酸化作用。许多研究表明磷脂特异性磷酸二酯酶磷脂酶D（PLD）参与许多G蛋白偶联受体的受体内吞和再循环，阿片样物质、甲酰或多巴胺受体。PLD水解磷脂（通常为磷脂酰胆碱（PC））的头基为磷脂酸（PA）和胆碱，并且被认为在细胞调节和受体运输中发挥重要功能。ADP-核糖基化和Rho家族的蛋白激酶和GTP结合蛋白调节两种哺乳动物PLD亚型1和2。哺乳动物和酵母PLD也被磷脂酰肌醇4，5-二磷酸有效刺激。PA产物是细胞内脂质信使。PLD和PA活性涉及广泛的生理过程和疾病，包括炎症、糖尿病、肿瘤发生或神经变性。本文综述了膜定位的G蛋白偶联受体功能的背景下，PLD的表征，结构和调控。
Prolonged agonist exposure of many G-protein coupled receptors induces a rapid receptor phosphorylation and uncoupling from G-proteins. Resensitization of these desensitized receptors requires endocytosis and subsequent dephosphorylation. Numerous studies show the involvement of phospholipid-specific phosphodiesterase phospholipase D (PLD) in the receptor endocytosis and recycling of many G-protein coupled receptors e.g., opioid, formyl or dopamine receptors. The PLD hydrolyzes the headgroup of a phospholipid, generally phosphatidylcholine (PC), to phosphatidic acid (PA) and choline and is assumed to play an important function in cell regulation and receptor trafficking. Protein kinases and GTP binding proteins of the ADP-ribosylation and Rho families regulate the two mammalian PLD isoforms 1 and 2. Mammalian and yeast PLD are also potently stimulated by phosphatidylinositol 4,5-bisphosphate. The PA product is an intracellular lipid messenger. PLD and PA activities are implicated in a wide range of physiological processes and diseases including inflammation, diabetes, oncogenesis or neurodegeneration. This review discusses the characterization, structure, and regulation of PLD in the context of membrane located G-protein coupled receptor function.