SPHINGOSINE 1-PHOSPHATE SIGNALING THROUGH THE G-PROTEIN-COUPLED RECEPTOR EDG-1

Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are stru cturally related lipid mediators that act on distinct G-protein-couple d receptors to evoke similar responses, including Ca2+ mobilization, a denylate cyclase inhibition, and mitogen activated protein (MAP) kinas e activation. However, little is still known about the respective rece ptors. A recently cloned putative LPA receptor (Vzg-1/Edg-2) is simila r to an orphan G(i)-coupled receptor termed Edg-1. Here we show that e xpression of Edg-1 in Sf9 and COS-7 cells results in inhibition of ade nylate cyclase and activation of MAP kinase (G(i)-mediated), but not C a2+ mobilization, in response to S1P. These responses are specific in that (i) S1P action is not mimicked by LPA, and (ii) Vzg-1/Edg-2 canno t substitute for Edg-1. Thus the Edg-1 receptor is capable of mediatin g a subset of the cellular responses to S1P.