Phospholipase D/phosphatidic acid signal transduction: Role and physiological significance in lung
Phospholipase D/phosphatidic acid signal transduction: Role and physiological significance in lung
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DOI：
10.1023/a:1015944828973
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发表时间：
2002-05-01
影响因子：
4.3
通讯作者：
Natarajan, V
中科院分区：
文献类型：
--
作者：
Cummings, R;Parinandi, N;Natarajan, V
磷脂酶D （Phospholipase D， PLD）是一种磷脂水解酶，可催化磷脂酰胆碱和其他膜磷脂水解成磷脂酸（磷脂酸）和胆碱。PLD在哺乳动物中普遍存在，是细胞内信号转导的关键酶。由激动剂或活性氧（ROS）介导的PLD1和PLD2亚型活化产生的PA随后可通过磷脂酶A(1)/A(2)或脂质磷酸磷酸酶转化为溶血opa （LPA）或二酰基甘油（DAG）。在肺上皮细胞和血管内皮细胞中，多种激动剂刺激PLD，包括Src激酶、p-38丝裂原活化蛋白激酶、钙和小G蛋白。源自PLD通路的PA具有第二信使功能。在内皮细胞中，PA调节NAD[P]H氧化酶活性和屏障功能。在气道上皮细胞中，鞘氨醇-1-磷酸和PA诱导的IL-8分泌和ERK1/2磷酸化受PA的调控。PA可代谢为LPA和DAG，分别作为第一信使和第二信使。哺乳动物细胞中的信号酶如Raf 1、蛋白激酶Czeta和I型磷脂酰肌醇-4-磷酸5激酶也受PA调节。因此，PA及其代谢产物在调节内皮细胞和上皮细胞功能中起核心作用。
Phospholipase D (PLD), a phospholipid phosphohydrolase, catalyzes the hydrolysis of phosphatidylcholine and other membrane phospholipids to phosphatidic acid (PA) and choline. PLD, ubiquitous in mammals, is a critical enzyme in intracellular signal transduction. PA generated by agonist- or reactive oxygen species (ROS)-mediated activation of the PLD1 and PLD2 isoforms can be subsequently converted to lysoPA (LPA) or diacylglycerol (DAG) by phospholipase A(1)/A(2) or lipid phosphate phosphatases. In pulmonary epithelial and vascular endothelial cells, a wide variety of agonists stimulate PLD and involve Src kinases, p-38 mitogen activated protein kinase, calcium and small G proteins. PA derived from the PLD pathway has second messenger functions. In endothelial cells, PA regulates NAD[P]H oxidase activity and barrier function. In airway epithelial cells, sphingosine-1-phosphate and PA-induced IL-8 secretion and ERK1/2 phosphorylation is regulated by PA. PA can be metabolized to LPA and DAG, which function as first- and second-messengers, respectively. Signaling enzymes such as Raf 1, protein kinase Czeta and type I phosphatidylinositol-4-phosphate 5-kinase are also regulated by PA in mammalian cells. Thus, PA and its metabolic products play a central role in modulating endothelial and epithelial cell functions.