Weeks R, Dowhan W, Shen H, Balantac N, Meengs B, Nudelman E, Leung D W
Cell Therapeutics, Inc., Seattle, WA 98119, USA.
DNA Cell Biol. 1997 Mar;16(3):281-9. doi: 10.1089/dna.1997.16.281.
Phosphatidic acid (PA) is a phospholipid involved in signal transduction and in glycerolipid biosynthesis. CDP-diacylglycerol synthase (CDS) or CTP:phosphatidate cytidylyltransferase (EC 2.7.7.41) catalyzes the conversion of PA to CDP-diacylglycerol (CDP-DAG), an important precursor for the synthesis of phosphatidylinositol, phosphatidylglycerol, and cardiolipin. We describe in this study the isolation and characterization of a human cDNA clone that encodes amino acid sequences homologous to Escherichia coli, yeast, and Drosophila CDS sequences. Expression of this human cDNA under the control of a GAL1 promoter in a null cds1 mutant yeast strain complements its growth defect and produces CDS activity when induced with galactose. Transfection of this cDNA into mammalian cells leads to increased CDS activity in cell-free extracts using an in vitro assay that measures the conversion of [alpha-32P]CTP to [32P]CDP-DAG. This increase in CDS activity also leads to increased secretion of tumor necrosis factor-alpha and interleukin-6 from endothelial ECV304 cells upon stimulation with interleukin-1beta, suggesting that CDS overexpression may amplify cellular signaling responses from cytokines.
磷脂酸（PA）是一种参与信号转导和甘油脂质生物合成的磷脂。CDP - 二酰基甘油合酶（CDS）或CTP：磷脂酸胞苷转移酶（EC 2.7.7.41）催化PA转化为CDP - 二酰基甘油（CDP - DAG），后者是合成磷脂酰肌醇、磷脂酰甘油和心磷脂的重要前体。我们在本研究中描述了一个人类cDNA克隆的分离和特性，该克隆编码与大肠杆菌、酵母和果蝇CDS序列同源的氨基酸序列。在GAL1启动子控制下，该人类cDNA在cds1突变酵母空菌株中的表达弥补了其生长缺陷，并在用半乳糖诱导时产生CDS活性。使用测量[α - 32P]CTP转化为[32P]CDP - DAG的体外测定法，将该cDNA转染到哺乳动物细胞中会导致无细胞提取物中CDS活性增加。CDS活性的这种增加还导致内皮ECV304细胞在受到白细胞介素 - 1β刺激后肿瘤坏死因子 - α和白细胞介素 - 6的分泌增加，这表明CDS过表达可能会放大细胞因子的细胞信号反应。
