Lysophosphatidic Acid

Surface LLP-1 Controls LPA Signaling

Science's STKE  12 Sep 2000:
Vol. 2000, Issue 49, pp. tw5
DOI: 10.1126/stke.2000.49.tw5

Lysophosphatidic acid (LPA) is a phospholipid growth factor found in serum. Many cell types respond to LPA through the activation of G protein-coupled receptors, EDG-2, EDG-4, or EDG-7. Xu et al. altered the cell surface levels of lipid phosphate phosphatase-1 (LLP-1) by overexpression or inhibition with antisense oligonucleotides and found that LPA degradation, LPA binding, and signal transduction through LPA-stimulated EDG-2 receptors were regulated. Overexpression of mouse LLP-1 in Rat2 fibroblasts increased LPA degradation, and decreased LPA binding to cells. Furthermore, increased LLP-1 blocked the LPA-induced decrease in cyclic adenosine monophosphate levels. Overexpression of LLP-1 also blocked LPA-induced increases in phospholipase D activity and mitogen-activated protein kinase activity and cell proliferation, as well as increases in intracellular Ca2+ concentration. Inhibition of the expression of endogenous LLP-1 with antisense oligonucleotides had the opposite effects as overexpression in Rat2 cells, confirming a role for LLP-1 in regulating cellular responsiveness to exogenous LPA.

Xu, J., Love, L.M., Singh, I., Zhang, Q.-X., Dewald, J., Wang, D.-A., Fischer, D.J., Tigyi, G., Berthiaume, L.G., Waggoner, D.W., and Brindley, D.N. (2000) Lipid phosphate phosphatase-1 and Ca2+ control lysophosphatidate signaling through EDG-2 receptors. J. Biol. Chem. 275: 27520-27530. [Abstract] [Full Text]