Identification of cDNAs encoding two G protein-coupled receptors for lysosphingolipids.

The structural similarity of lysosphingolipids to lysophosphatidic acid (LPA) prompted a sequence-based search for lysosphingolipid receptors using cDNA sequence of the Edg2 human LPA receptor. Two closely related G protein-coupled receptors, rat H218 and human Edg3, are highly similar to Edg2. When overexpressed in Jurkat cells, H218 and Edg3 activated serum response element-driven transcriptional reporter gene in response to sphingosine 1-phosphate (S1P), dihydro-S1P and sphingosylphosphorylcholine, but not to LPA. H218 and Edg3 expressed in Xenopus oocytes conferred responsiveness to S1P and dihydro-S1P in agonist-triggered 45Ca2+ efflux. Therefore, H218 and Edg3 are functional receptors for S1P and perhaps other closely related lysosphingolipids.