Sphingosine-1-Phosphate as a Ligand for the G Protein-Coupled Receptor EDG-1

• DOI: 10.1126/science.279.5356.1552
• Publication Date: 2002-07-27T09:42:47Z
• Authors: Menq-Jer Lee; James R. Van Broc...; Shobha Thangada; Catherine H. Liu; Arthur R. Hand; Ramil Menzeleev; Sarah Spiegel; Timothy Hla
• Keywords: S1PR1; Adherens junction; Jurkat cells; Sphingosine-1-phosphate receptor

The sphingolipid metabolite sphingosine-1–phosphate (SPP) has been implicated as a second messenger in cell proliferation and survival. However, many of its biological effects are due to binding unidentified receptors on the surface. SPP activated heterotrimeric guanine nucleotide protein (G protein)–coupled orphan receptor EDG-1, originally cloned Endothelial Differentiation Gene – 1 . EDG-1 bound with high affinity (dissociation constant = 8.1 nM) specificity. Overexpression induced exaggerated cell-cell aggregation, enhanced expression cadherins, formation well-developed adherens junctions manner dependent small Rho.