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Lipid phosphate phosphatase-1 regulates lysophosphatidic acid- and platelet-derived-growth-factor-induced cell migration

Pyne, N.J. and Long, J.S.L. and Yokoyama, K. and Tigyi, G. and Pyne, S. (2006) Lipid phosphate phosphatase-1 regulates lysophosphatidic acid- and platelet-derived-growth-factor-induced cell migration. Biochemical Journal, 394. pp. 495-500. ISSN 0264-6021

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Abstract

LPPs (lipid phosphate phosphatases) are members of a family of enzymes that catalyse the dephosphorylation of lipid phosphates. The only known form of regulation of this family of enzymes is via de novo expression of LPP isoforms in response to growth factors. In this respect, we evaluated the effect of moderate increases in the expression of recombinant LPP1 on signal transduction by both G-protein-coupled receptors and receptor tyrosine kinases. We present evidence for a novel role of LPP1 in reducing PDGF (platelet-derived growth factor)- and lysophosphatidic acid-induced migration of embryonic fibroblasts. We demonstrate that the overexpression of LPP1 inhibits cell migration by reducing the PDGF-induced activation of p42/p44 MAPK (mitogen-activated protein kinase). This appears to occur via a mechanism that involves the LPP1-induced down-regulation of typical PKC (protein kinase C) isoform(s), which are normally required for PDGF-induced activation of p42/p44 MAPK and migration. In this regard, DAG (diacylglycerol) levels are high and sustained in cells overexpressing LPP1, suggesting a dynamic interconversion of phosphatidic acid into DAG by LPP1. This may account for the effects of LPP1 on cell migration, as sustained DAG is known to down-regulate PKC isoforms in cells. Therefore the physiological changes in the expression levels of LPP1 might represent a heterologous desensitization mechanism for attenuating PKC-mediated signalling and regulation of cell migration.

Item type: Article
ID code: 10411
Keywords: cell migration, lipid phosphate phosphatase, lysophosphatidic acid, p42/p44 mitogen-activated protein kinase (MAPK) , phosphatidic acid, platelet-derived growth factor, Pharmacy and materia medica, Biochemistry, Cell Biology, Molecular Biology
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Strathprints Administrator
    Date Deposited: 17 Nov 2011 13:59
    Last modified: 04 Sep 2014 20:15
    URI: http://strathprints.strath.ac.uk/id/eprint/10411

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