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

Science  06 Mar 1998:
Vol. 279, Issue 5356, pp. 1552-1555
DOI: 10.1126/science.279.5356.1552

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Abstract

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 to unidentified receptors on the cell surface. SPP activated the heterotrimeric guanine nucleotide binding protein (G protein)–coupled orphan receptor EDG-1, originally cloned asEndothelial Differentiation Gene1. EDG-1 bound SPP with high affinity (dissociation constant = 8.1 nM) and high specificity. Overexpression of EDG-1 induced exaggerated cell-cell aggregation, enhanced expression of cadherins, and formation of well-developed adherens junctions in a manner dependent on SPP and the small guanine nucleotide binding protein Rho.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: hla{at}sun.uchc.edu

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