Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases

Amanda M. Gellett, Yugesh Kharel, Manjula Sunkara, Andrew J. Morris, Kevin R. Lynch

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish
Pages (from-to)758-763
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - Jun 15 2012

Bibliographical note

Funding Information:
The authors thank Kaoru Goto, M.D., Ph.D. for DGKα, DGKβ, and DGKγ cDNA; Fumio Sakane, Ph.D. for DGKδ1 and DGKδ2 cDNA and anti-DGKα, anti-DGKβ, anti-DGKγ, antibodies; and Matthew Topham, M.D. for DGKζ and DGKι cDNA. This work was supported by the NIH (R01 GM067958 K.R.L, T32 GM007055 A.M.G and R01 GM50388 and P20 RR021954 A.J.M).


  • Alkyl lysophosphatidic acid
  • Alkylglycerol phosphate
  • Diacylglycerol kinase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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