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J. Biol. Chem., Vol. 276, Issue 7, 4611-4621, February 16, 2001
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From the Departments of Lysophosphatidic acid (LPA) is an extracellular
signaling mediator with a broad range of cellular responses. Three
G-protein-coupled receptors (Edg-2, -4, and -7) have been identified as
receptors for LPA. In this study, the ectophosphatase lipid phosphate
phosphatase 1 (LPP1) has been shown to down-regulate LPA-mediated
mitogenesis. Furthermore, using degradation-resistant phosphonate
analogs of LPA and stereoselective agonists of the Edg receptors we
have demonstrated that the mitogenic and platelet aggregation responses to LPA are independent of Edg-2, -4, and -7. Specifically, we found
that LPA degradation is insufficient to account for the decrease in LPA
potency in mitogenic assays, and the stereoselectivity observed at the
Edg receptors is not reflected in mitogenesis. Additionally, RH7777
cells, which are devoid of Edg-2, -4, and -7 receptor mRNA, have a
mitogenic response to LPA and LPA analogs. Finally, we have determined
that the ligand selectivity of the platelet aggregation response is
consistent with that of mitogenesis, but not with Edg-2, -4, and
-7.
Lysophosphatidic Acid-induced Mitogenesis Is Regulated by Lipid
Phosphate Phosphatases and Is Edg-receptor Independent*
§,
,,
Biochemistry,
¶ Chemistry, and Pharmacology, University of Virginia
Health Sciences Center, Charlotte, Virginia 22908
*
This work was supported by Grants R01-GM52722 (to K. R. L.
and T. L. M.) and F31-DA05927 (to S. B. H.) from the National
Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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