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Blood, Vol. 95 No. 8 (April 15), 2000:
pp. 2624-2629
Sphingosine-1-phosphate is a ligand for the G protein-coupled
receptor EDG-6
James R. Van Brocklyn,
Markus H. Gräler,
Günter Bernhardt,
John P. Hobson,
Martin Lipp, and
Sarah Spiegel
From the Department of Biochemistry and Molecular Biology,
Georgetown University Medical Center, Washington, DC; and Max
Delbrück Center for Molecular Medicine, Department of Tumor
Genetics and Immunogenetics, Berlin, Germany.
EDG-6 is a recently cloned member of the endothelial differentiation
gene (EDG) G protein-coupled receptor family that is expressed in
lymphoid and hematopoietic tissue and in the lung. Homology of EDG-6 to
the known sphingosine-1-phosphate (SPP) receptors EDG-1, EDG-3, and
EDG-5 and lysophosphatidic acid (LPA) receptors EDG-2 and EDG-4
suggested that its ligand may be a lysophospholipid or
lysosphingolipid. We examined the binding of [32P]SPP to
HEK293 cells, transiently transfected with cDNA encoding EDG-6. Binding
of [32P]SPP was saturable, demonstrating high affinity
(KD = 63 nmol/L). Binding was also specific for SPP, as
only unlabeled SPP and sphinganine-1-phosphate, which lacks the trans
double bond at the 4 position, potently displaced radiolabeled SPP. LPA
did not compete for binding of SPP at any concentration tested, whereas
sphingosylphosphorylcholine competed for binding to EDG-6, but only at
very high concentrations. In addition, SPP activated extracellular
signal-regulated kinase (Erk) in EDG-6 transfected cells in a pertussis
toxin-sensitive manner. These results indicate that EDG-6 is a high
affinity receptor for SPP, which couples to a Gi/o protein,
resulting in the activation of growth-related signaling pathways.
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|
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|
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|
|
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|
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|
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|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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54(2):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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60(6):
1173 - 1180.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Science,
November 30, 2001;
294(5548):
1875 - 1878.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. A. Contos, I. Ishii, and J. Chun
Lysophosphatidic Acid Receptors
Mol. Pharmacol.,
April 13, 2001;
58(6):
1188 - 1196.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
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Cardiovasc Res,
February 16, 2001;
49(3):
588 - 599.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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J. Biol. Chem.,
December 8, 2000;
275(50):
39379 - 39384.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. B. Hooks, W. L. Santos, D.-S. Im, C. E. Heise, T. L. Macdonald, and K. R. Lynch
Lysophosphatidic Acid-induced Mitogenesis Is Regulated by Lipid Phosphate Phosphatases and Is Edg-receptor Independent
J. Biol. Chem.,
February 9, 2001;
276(7):
4611 - 4621.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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J. Biol. Chem.,
April 6, 2001;
276(15):
11830 - 11837.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Siehler, Y. Wang, X. Fan, R. T. Windh, and D. R. Manning
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J. Biol. Chem.,
December 21, 2001;
276(52):
48733 - 48739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Ishii, B. Friedman, X. Ye, S. Kawamura, C. McGiffert, J. J. A. Contos, M. A. Kingsbury, G. Zhang, J. H. Brown, and J. Chun
Selective Loss of Sphingosine 1-Phosphate Signaling with No Obvious Phenotypic Abnormality in Mice Lacking Its G Protein-coupled Receptor, LPB3/EDG-3
J. Biol. Chem.,
August 31, 2001;
276(36):
33697 - 33704.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D.-a. Wang, Z. Lorincz, D. L. Bautista, K. Liliom, G. Tigyi, and A. L. Parrill
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276(52):
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[Full Text]
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|
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