1. Academic Validation
  2. Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases

Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases

  • Biochem Biophys Res Commun. 2012 Jun 15;422(4):758-63. doi: 10.1016/j.bbrc.2012.05.077.
Amanda M Gellett 1 Yugesh Kharel Manjula Sunkara Andrew J Morris Kevin R Lynch
Affiliations

Affiliation

  • 1 Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
Abstract

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 DGKα. 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 DGKα contributes significantly to the production of alkyl-LPA in SKOV-3 cells and identifying cross-talk between the sphingolipid and glycerol lipid pathways.

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