Diacylglycerol kinase zeta

Definition

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 (Probable). Does not exhibit an acyl chain-dependent substrate specificity among diacylglycerol species. Can also phosphorylate 1-alkyl-2-acylglycerol in vitro but less efficiently and with a preference for alkylacylglycerols containing an arachidonoyl group. The biological processes it is involved in include T cell activation since it negatively regulates T-cell receptor signaling which is in part mediated by diacylglycerol (By similarity). By generating phosphatidic acid, stimulates PIP5KIA activity which regulates actin polymerization. Through the same mechanism could also positively regulate insulin-induced translocation of SLC2A4 to the cell membrane (By similarity).; [Isoform 1]: Regulates RASGRP1 activity.; [Isoform 2]: Does not regulate RASGRP1 activity.

References:

[1]. M K Topham, et al. Diacylglycerol kinase zeta regulates Ras activation by a novel mechanism. J Cell Biol. 2001 Mar 19;152(6):1135-43. [Content Brief]

[2]. M Bunting, et al. Molecular cloning and characterization of a novel human diacylglycerol kinase zeta. J Biol Chem. 1996 Apr 26;271(17):10230-6. [Content Brief]

[3]. L Ding, et al. Alternative splicing of the human diacylglycerol kinase zeta gene in muscle. Proc Natl Acad Sci U S A. 1997 May 27;94(11):5519-24. [Content Brief]

[4]. Amanda M Gellett, et al. Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases. Biochem Biophys Res Commun. 2012 Jun 15;422(4):758-63. [Content Brief]

[5]. 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]

[6]. Bai Luo, et al. Diacylglycerol kinase zeta regulates phosphatidylinositol 4-phosphate 5-kinase Ialpha by a novel mechanism. Cell Signal. 2004 Aug;16(8):891-7. [Content Brief]

[7]. Richard M Epand, et al. Substrate chirality and specificity of diacylglycerol kinases and the multisubstrate lipid kinase. Biochemistry. 2007 Dec 11;46(49):14225-31. [Content Brief]

[8]. 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]

[9]. 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]

[10]. 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]

生物医学辞典

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