Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases

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• 作者：Amanda M. Gellett^a ; Yugesh Kharel^a ; Manjula Sunkara^b ; Andrew J. Morris^b ; Kevin R. Lynch^a ; ^{krl2z@virginia.edu}
• 关键词：LPA ; lysophosphatidic acid ; ATX ; autotaxin ; 2-AcMAGE ; 2-acetyl monoalkylglycerol ether ; 1-O-hexadecyl-sn-2-acetyl glycerol ; MAGE ; monoalkylglycerol ether ; 1-O-hexadecyl-sn-glycerol ; MAG ; monoacylglycerol ; AGK/MuLK ; acylglycerol kinase/multiple lipid subst
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 出版时间：15 June, 2012
• 年：2012
• 卷：422
• 期：4
• 页码：758-763
• 全文大小：382 K

文摘

Lysophosphatidic acid (LPA) designates a family of bioactive phosphoglycerides that differ in the length and degree of saturation of their radyl chain. Additional diversity is provided by the linkage of the radyl chain to glycerol: acyl, alkyl, or alk-1-enyl. Acyl-LPAs are the predominate species in tissues and biological fluids. Alkyl-LPAs exhibit distinct pharmacodynamics at LPA receptors, potently drive platelet aggregation, and contribute to ovarian cancer aggressiveness. Multiple biosynthetic pathways exist for alkyl-LPA production. Herein we report that diacylglycerol kinases (DGKs) contribute to cell-associated alkyl-LPA production involving phosphorylation of 1-alkyl-2-acetyl glycerol and document the biosynthesis of alkyl-LPA by DGKs in SKOV-3 ovarian cancer cells, specifically identifying the contribution of DGK¦Á. Concurrently, we discovered that treating SKOV-3 ovarian cancer cell with a sphingosine analog stimulates conversion of exogenous 1-alkyl-2-acetyl glycerol to alkyl-LPA, indicating that DGK¦Á contributes significantly to the production of alkyl-LPA in SKOV-3 cells and identifying cross-talk between the sphingolipid and glycerol lipid pathways.