Role of phospholipase D in agonist-stimulated lysophosphatidic acid synthesis by ovarian cancer cells

Céline Luquain, Anurag Singh, Lixin Wang, Vishwanathan Natarajan, Andrew J. Morris

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Lysophosphatidic acid (LPA) is a receptor-active lipid mediator with a broad range of biological effects. Ovarian cancer cells synthesize LPA, which promotes their motility, growth, and survival. We show that a murine homolog of a human protein previously reported to hydrolyze LPA is a highly selective detergent-stimulated LPA phosphatase that can be used to detect and quantitate LPA. Use of this protein in novel enzymatic assay demonstrates that SK-OV-3 ovarian cancer cells release physiologically relevant levels of biologically active LPA into the extracellular space. LPA release is markedly increased by nucleotide agonists acting through a P2Y4 purinergic receptor. Promotion of LPA formation by nucleotides is accompanied by stimulation of phospholipase D (PLD) activity. Overexpression of both PLD1 and PLD2 in SK-OV-3 cells produces active enzymes, but only overexpression of PLD2 results in significant amplification of both nucleotide-stimulated PLD activity and LPA production. SK-OV-3 cells express and secrete a phospholipase A2 activity that can generate LPA from the lipid product of PLD, phosphatidic acid. Our results identify a novel role for nucleotides in the regulation of ovarian cancer cells and suggest an indirect but critical function for PLD2 in agonist-stimulated LPA production.

Original languageEnglish
Pages (from-to)1963-1975
Number of pages13
JournalJournal of Lipid Research
Issue number10
StatePublished - Oct 2003


  • Adenosine 5′-triphosphate
  • Enzymatic assay
  • Lysophosphatidic acid phosphatase
  • Phosphatidic acid
  • Phospholipase A
  • Phospholipase D1/phospholipase D2 isoforms
  • Purinergic receptor
  • Uridine 5′ triphosphate

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


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