HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M300188-JLR200v1 44/10/1963    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Luquain, C. Articles by Morris, A. J. Search for Related Content PubMed PubMed Citation Articles by Luquain, C. Articles by Morris, A. J. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 44, 1963-1975, October 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

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

Céline Luquain^*, Anurag Singh^*, Lixin Wang, Vishwanathan Natarajan and Andrew J. Morris^1,*

^* Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7090
Department of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, MD 21224

¹ To whom correspondence should be addressed. e-mail: ajmorris{at}med.unc.edu

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.

Abbreviations: ARF, ADP-ribosylation factor; C1P, ceramide 1-phosphate; LPA, lysophosphatidic acid; LPAP, lysophosphatidic acid phosphatase; LPP, lipid phosphate phosphatase; PA, phosphatidic acid; PC, phosphatidylcholine; PI(4,5)P₂, phosphatidylinositol 4,5-bisphosphate; PLA₂, phospholipase A₂; PLC, phospholipase C; PLD, phospholipase D; PtdBut, phosphatidylbutanol; S1P, sphingosine 1-phosphate

Supplementary key words lysophosphatidic acid phosphatase • enzymatic assay • uridine 5' triphosphate • adenosine 5'-triphosphate • phospholipase D1/phospholipase D2 isoforms • purinergic receptor • phospholipase A₂ • phosphatidic acid • phosphatidylcholine-specific phospholipase D

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				X. Ye Lysophospholipid signaling in the function and pathology of the reproductive system Hum. Reprod. Update, September 1, 2008; 14(5): 519 - 536. [Abstract] [Full Text] [PDF]

				A. Giganti, M. Rodriguez, B. Fould, N. Moulharat, F. Coge, P. Chomarat, J.-P. Galizzi, P. Valet, J.-S. Saulnier-Blache, J. A. Boutin, et al. Murine and Human Autotaxin {alpha}, {beta}, and {gamma} Isoforms: GENE ORGANIZATION, TISSUE DISTRIBUTION, AND BIOCHEMICAL CHARACTERIZATION J. Biol. Chem., March 21, 2008; 283(12): 7776 - 7789. [Abstract] [Full Text] [PDF]

				E. S. Jeon, H. J. Moon, M. J. Lee, H. Y. Song, Y. M. Kim, M. Cho, D.-S. Suh, M.-S. Yoon, C. L. Chang, J. S. Jung, et al. Cancer-Derived Lysophosphatidic Acid Stimulates Differentiation of Human Mesenchymal Stem Cells to Myofibroblast-Like Cells Stem Cells, March 1, 2008; 26(3): 789 - 797. [Abstract] [Full Text] [PDF]

				F.-q. Wang, Y. Smicun, N. Calluzzo, and D. A. Fishman Inhibition of Matrilysin Expression by Antisense or RNA Interference Decreases Lysophosphatidic Acid-Induced Epithelial Ovarian Cancer Invasion Mol. Cancer Res., November 1, 2006; 4(11): 831 - 841. [Abstract] [Full Text] [PDF]

				E. Iorio, D. Mezzanzanica, P. Alberti, F. Spadaro, C. Ramoni, S. D'Ascenzo, D. Millimaggi, A. Pavan, V. Dolo, S. Canevari, et al. Alterations of Choline Phospholipid Metabolism in Ovarian Tumor Progression Cancer Res., October 15, 2005; 65(20): 9369 - 9376. [Abstract] [Full Text] [PDF]

				H. Li, X. Ye, C. Mahanivong, D. Bian, J. Chun, and S. Huang Signaling Mechanisms Responsible for Lysophosphatidic Acid-induced Urokinase Plasminogen Activator Expression in Ovarian Cancer Cells J. Biol. Chem., March 18, 2005; 280(11): 10564 - 10571. [Abstract] [Full Text] [PDF]