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

Lysophosphatidic acid (LPA) and sphingosine-l-phosphate (SIP) are produced during cell activation and have multiple effects on cells. A family of seve n transmembrane-spanning domain G-protein-coupled receptors, named Edg, med iate these effects of LPA and SIP. In this study, transient overexpression of Edg-2 sensitized MG63 human osteosarcoma cells to both LPA- and S1P-medi ated stimulation of fibronectin matrix deposition and actin stress fiber fo rmation. Both lipids were active in the 1-20 nM concentration range on cell s transfected with Edg-2 as compared to the 10-200 nM range on mock-transfe cted cells. The signaling pathway for matrix deposition by Edg-2-transfecte d cells was Rho dependent. Overexpression of Edg-2 also caused a tenfold de crease in the concentration of either LPA or S1P that activated MAPKinase ( Erk1/2) in MG63 cells. LPA- or S1P-stimulated activation of Erk1/2 was Gi d ependent. These results indicate that, in MG63 cells, Edg-2 mediates actin stress fiber formation, fibronectin matrix assembly, and MAPKinase activati on in response to either LPA or SIP.