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Differential stimulation of signaling pathways initiated by Edg-2 in response to lysophosphatidic acid or sphingosine-1-phosphate

Author:
Peyruchaud*, **, O., Mosher, D. F.
Source:
Cellular and molecular life sciences 2000 v.57 no.7 pp. 1109-1116
ISSN:
1420-682X
Subject:
G-protein coupled receptors, actin, fibronectins, humans, lipids, osteosarcoma, signal transduction
Abstract:
Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are produced during cell activation and have multiple effects on cells. A family of seven transmembrane-spanning domain G-protein-coupled receptors, named Edg, mediate these effects of LPA and S1P. In this study, transient overexpression of Edg-2 sensitized MG63 human osteosarcoma cells to both LPA- and S1P-mediated stimulation of fibronectin matrix deposition and actin stress fiber formation. Both lipids were active in the 1–20 nM concentration range on cells transfected with Edg-2 as compared to the 10–200 nM range on mock-transfected cells. The signaling pathway for matrix deposition by Edg-2-transfected cells was Rho dependent. Overexpression of Edg-2 also caused a tenfold decrease in the concentration of either LPA or S1P that activated MAPKinase (Erk1/2) in MG63 cells. LPA- or S1P-stimulated activation of Erkl/2 was Gi dependent. These results indicate that, in MG63 cells, Edg-2 mediates actin stress fiber formation, fibronectin matrix assembly, and MAPKinase activation in response to either LPA or S1P.
Agid:
4372691