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

Author:

Lee Menq-Jer123,Van Brocklyn James R.123,Thangada Shobha123,Liu Catherine H.123,Hand Arthur R.123,Menzeleev Ramil123,Spiegel Sarah123,Hla Timothy123

Affiliation:

1. M.-J. Lee, S. Thangada, C. H. Liu, T. Hla, Department of Physiology, University of Connecticut School of Medicine, Farmington, CT 06030, USA.

2. J. R. Van Brocklyn, R. Menzeleev, S. Spiegel, Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20007, USA.

3. A. R. Hand, Department of Pediatric Dentistry, University of Connecticut Health Center, Farmington, CT 06030, USA.

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 as Endothelial 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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