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Sphingosine-1-Phosphate as a Ligand for the G Protein-Coupled Receptor EDG-1
Menq-Jer Lee,*
James R. Van Brocklyn,*
Shobha Thangada,
Catherine H. Liu,
Arthur R. Hand,
Ramil Menzeleev,
Sarah Spiegel,*
Timothy Hla*
The sphingolipid metabolite sphingosine-1-phosphate (SPP) has been
implicated as a second messenger in cell proliferationand survival.
However, many of its biological effects are dueto binding to
unidentified receptors on the cell surface. SPPactivated the
heterotrimeric guanine nucleotide binding protein(G
protein)-coupled orphan receptor EDG-1, originally cloned asEndothelial Differentiation Gene-1. EDG-1 bound
SPP with highaffinity (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-developedadherens junctions in a manner dependent on SPP and the
smallguanine nucleotide binding protein Rho.
M.-J. Lee, S. Thangada, C. H. Liu, T. Hla, Department of
Physiology, University of Connecticut School of Medicine, Farmington,
CT 06030, USA.
J. R. Van Brocklyn, R. Menzeleev, S. Spiegel, Department of
Biochemistry and Molecular Biology, Georgetown University Medical
Center, Washington, DC 20007, USA.
A. R. Hand, Department of Pediatric Dentistry, University of
Connecticut Health Center, Farmington, CT 06030, USA.
*
These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail:
hla{at}sun.uchc.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
LETTERS
Owen N. Witte, Janusz H. Kabarowski, Yan Xu, Lu Q. Le, and Kui Zhu (14 January 2005) Science307 (5707), 206b.
[DOI: 10.1126/science.307.5707.206b] |Full Text »|PDF »
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F. Coussin, R. H. Scott, A. Wise, and G. F. Nixon (2002)
Circ. Res.
91, 151-157
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Activation of second messenger pathways in alveolar macrophages by endotoxin.
Ceramide Kinase, a Novel Lipid Kinase. MOLECULAR CLONING AND FUNCTIONAL CHARACTERIZATION.
M. Sugiura, K. Kono, H. Liu, T. Shimizugawa, H. Minekura, S. Spiegel, and T. Kohama (2002)
J. Biol. Chem.
277, 23294-23300
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Sphingosine 1-Phosphate Induces Membrane Ruffling and Increases Motility of Human Umbilical Vein Endothelial Cells via Vascular Endothelial Growth Factor Receptor and CrkII.
A. Endo, K.-I. Nagashima, H. Kurose, S. Mochizuki, M. Matsuda, and N. Mochizuki (2002)
J. Biol. Chem.
277, 23747-23754
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International Union of Pharmacology. XXXIV. Lysophospholipid Receptor Nomenclature.
J. Chun, E. J. Goetzl, T. Hla, Y. Igarashi, K. R. Lynch, W. Moolenaar, S. Pyne, and G. Tigyi (2002)
Pharmacol. Rev.
54, 265-269
|Abstract »|Full Text »|PDF »
Cell Type-specific Localization of Human Cardiac S1P Receptors.
D. Mazurais, P. Robert, B. Gout, I. Berrebi-Bertrand, M. P. Laville, and T. Calmels (2002)
J. Histochem. Cytochem.
50, 661-670
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Sphingosine 1-Phosphate, Present in Serum-derived Lipoproteins, Activates Matriptase.
C. Benaud, M. Oberst, J. P. Hobson, S. Spiegel, R. B. Dickson, and C.-Y. Lin (2002)
J. Biol. Chem.
277, 10539-10546
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