Goto Kaoru, Hozumi Yasukazu, Nakano Tomoyuki, Saino-Saito Sachiko, Martelli Alberto M
Department of Anatomy and Cell Biology, Yamagata University School of Medicine.
Tohoku J Exp Med. 2008 Mar;214(3):199-212. doi: 10.1620/tjem.214.199.
Diacylglycerol kinase (DGK) metabolizes diacylglycerol (DG), a glycerolipid containing two acyl chains, to convert phosphatidic acid. DG is produced through phosphoinositide turnover within the membrane and is well known to act as a second messenger that modulates the activity of protein kinase C in the cellular signal transduction. Recent studies have revealed that DG also activates several proteins, including Ras guanine-nucleotide releasing protein and ion channels such as transient receptor potential proteins. Therefore, DGK is thought to participate in a number of signaling cascades by modulating levels of DG. Previous studies have disclosed that DGK is composed of a family of the isozymes, which differ in the structure, enzymological property, gene expression and localization, subcellular localization, and binding molecules. The present review focuses on the stories of phosphoinositide turnover and DG, including historical views, structural features, metabolism, and relevant cellular phenomena, together with the characteristics of DGK isozymes and the pathophysiological findings on animal studies using knockout mice and models for human diseases. Now it is being revealed that the structural and functional diversity and heterogeneity of and around DGK support the proper arrangement of the complex signal transduction machinery.
二酰基甘油激酶（DGK）将二酰基甘油（DG，一种含有两条酰基链的甘油脂质）代谢为磷脂酸。DG通过膜内磷酸肌醇周转产生，并且众所周知它作为第二信使在细胞信号转导中调节蛋白激酶C的活性。最近的研究表明，DG还能激活多种蛋白质，包括Ras鸟嘌呤核苷酸释放蛋白和离子通道，如瞬时受体电位蛋白。因此，DGK被认为通过调节DG水平参与多种信号级联反应。先前的研究表明，DGK由一组同工酶组成，它们在结构、酶学性质、基因表达与定位、亚细胞定位以及结合分子方面存在差异。本综述聚焦于磷酸肌醇周转和DG的相关内容，包括历史观点、结构特征、代谢以及相关细胞现象，同时还介绍了DGK同工酶的特点以及使用基因敲除小鼠和人类疾病模型进行动物研究的病理生理学发现。现在有研究表明，DGK及其周围的结构和功能多样性与异质性支持了复杂信号转导机制的合理安排。
