Shirai Yasuhito, Saito Naoaki
Laboratory of Chemistry and Utilization of Animal Production Resources, Applied Chemistry in Bioscience Division, Graduate School of Agricultural Science, Kobe University, Rokkodai-cho 1-1, Nada-ku, 657-8501 Kobe, Japan.
J Biomed Sci. 2014 Apr 7;21(1):28. doi: 10.1186/1423-0127-21-28.
Diacylglycerol kinase (DGK) is a lipid kinase converting diacylglycerol to phosphatidic acid, and regulates many enzymes including protein kinase C, phosphatidylinositol 4-phosphate 5-kinase, and mTOR. To date, ten mammalian DGK subtypes have been cloned and divided into five groups, and they show subtype-specific tissue distribution. Therefore, each DGK subtype is thought to be involved in respective cellular responses by regulating balance of the two lipid messengers, diacylglycerol and phosphatidic acid. Indeed, the recent researches using DGK knockout mice have clearly demonstrated the importance of DGK in the immune system and its pathophysiological roles in heart and insulin resistance in diabetes. Especially, most subtypes show high expression in brain with subtype specific regional distribution, suggesting that each subtype has important and unique functions in brain. Recently, neuronal functions of some DGK subtypes have accumulated. Here, we introduce DGKs with their structural motifs, summarize the enzymatic properties and neuronal functions, and discuss the possibility of DGKs as a therapeutic target of the neuronal diseases.
二酰基甘油激酶（DGK）是一种将二酰基甘油转化为磷脂酸的脂质激酶，可调节包括蛋白激酶C、磷脂酰肌醇4-磷酸5-激酶和mTOR在内的多种酶。迄今为止，已克隆出十种哺乳动物DGK亚型并分为五组，它们表现出亚型特异性的组织分布。因此，每种DGK亚型被认为通过调节二酰基甘油和磷脂酸这两种脂质信使的平衡参与各自的细胞反应。事实上，最近使用DGK基因敲除小鼠的研究清楚地证明了DGK在免疫系统中的重要性及其在心脏和糖尿病胰岛素抵抗中的病理生理作用。特别是，大多数亚型在大脑中高表达且具有亚型特异性区域分布，这表明每种亚型在大脑中具有重要且独特的功能。最近，一些DGK亚型的神经元功能已有积累。在此，我们介绍具有其结构基序的DGK，总结其酶学性质和神经元功能，并讨论DGK作为神经元疾病治疗靶点的可能性。
