Diacylglycerol kinase epsilon

Definition:

Membrane-bound diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids. Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes. Also plays an important role in the biosynthesis of complex lipids. Displays specificity for diacylglycerol substrates with an arachidonoyl acyl chain at the sn-2 position, with the highest activity toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol the main diacylglycerol intermediate within the phosphatidylinositol turnover cycle. Can also phosphorylate diacylglycerol substrates with a linoleoyl acyl chain at the sn-2 position but much less efficiently.

References:

[1]. Yulia V Shulga, et al. Study of arachidonoyl specificity in two enzymes of the PI cycle. J Mol Biol. 2011 Jun 3;409(2):101-12. [Content Brief]

[2]. Fatih Ozaltin, et al. DGKE variants cause a glomerular microangiopathy that mimics membranoproliferative GN. J Am Soc Nephrol. 2013 Feb;24(3):377-84. [Content Brief]

[3]. Yulia V Shulga, et al. Substrate specificity of diacylglycerol kinase-epsilon and the phosphatidylinositol cycle. FEBS Lett. 2011 Dec 15;585(24):4025-8. [Content Brief]

[4]. Michael Lung, et al. Diacylglycerol kinase epsilon is selective for both acyl chains of phosphatidic acid or diacylglycerol. J Biol Chem. 2009 Nov 6;284(45):31062-73. [Content Brief]

[5]. Richard M Epand, et al. The alpha isoform of diacylglycerol kinase exhibits arachidonoyl specificity with alkylacylglycerol. Biochemistry. 2004 Nov 23;43(46):14778-83. [Content Brief]

[6]. W Tang, et al. Molecular cloning of a novel human diacylglycerol kinase highly selective for arachidonate-containing substrates. J Biol Chem. 1996 Apr 26;271(17):10237-41. [Content Brief]

[7]. Mayu Sato, et al. Evaluations of the selectivities of the diacylglycerol kinase inhibitors R59022 and R59949 among diacylglycerol kinase isozymes using a new non-radioactive assay method. Pharmacology. 2013;92(1-2):99-107. [Content Brief]

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