|
|
 Previous Article | Table of Contents | Next Article 
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.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
X. Ye
Lysophospholipid signaling in the function and pathology of the reproductive system
Hum. Reprod. Update,
June 25, 2008;
(2008)
dmn023v2.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Wang, M.-C. Huang, and E. J. Goetzl
Type 1 Sphingosine 1-Phosphate G Protein-Coupled Receptor (S1P1) Mediation of Enhanced IL-4 Generation by CD4 T Cells from S1P1 Transgenic Mice
J. Immunol.,
April 15, 2007;
178(8):
4885 - 4890.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D.-J. Jun, J.-H. Lee, B.-H. Choi, T.-K. Koh, D.-C. Ha, M.-W. Jeong, and K.-T. Kim
Sphingosine-1-Phosphate Modulates Both Lipolysis and Leptin Production in Differentiated Rat White Adipocytes
Endocrinology,
December 1, 2006;
147(12):
5835 - 5844.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ozbay, A. Rowan, A. Leon, P. Patel, and M. B. Sewer
Cyclic Adenosine 5'-Monophosphate-Dependent Sphingosine-1-Phosphate Biosynthesis Induces Human CYP17 Gene Transcription by Activating Cleavage of Sterol Regulatory Element Binding Protein 1
Endocrinology,
March 1, 2006;
147(3):
1427 - 1437.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A. Maghazachi
Insights into Seven and Single Transmembrane-Spanning Domain Receptors and Their Signaling Pathways in Human Natural Killer Cells
Pharmacol. Rev.,
September 1, 2005;
57(3):
339 - 357.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. Graler, M.-C. Huang, S. Watson, and E. J. Goetzl
Immunological Effects of Transgenic Constitutive Expression of the Type 1 Sphingosine 1-Phosphate Receptor by Mouse Lymphocytes
J. Immunol.,
February 15, 2005;
174(4):
1997 - 2003.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Argraves, B. A. Wilkerson, W. S. Argraves, P. A. Fleming, L. M. Obeid, and C. J. Drake
Sphingosine-1-phosphate Signaling Promotes Critical Migratory Events in Vasculogenesis
J. Biol. Chem.,
November 26, 2004;
279(48):
50580 - 50590.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D.-S. Im
Discovery of new G protein-coupled receptors for lipid mediators
J. Lipid Res.,
March 1, 2004;
45(3):
410 - 418.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. G. Radu, L. V. Yang, M. Riedinger, M. Au, and O. N. Witte
T cell chemotaxis to lysophosphatidylcholine through the G2A receptor
PNAS,
January 6, 2004;
101(1):
245 - 250.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Sanchez, T. Estrada-Hernandez, J.-H. Paik, M.-T. Wu, K. Venkataraman, V. Brinkmann, K. Claffey, and T. Hla
Phosphorylation and Action of the Immunomodulator FTY720 Inhibits Vascular Endothelial Cell Growth Factor-induced Vascular Permeability
J. Biol. Chem.,
November 21, 2003;
278(47):
47281 - 47290.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Takeya, E. C. Gabazza, S. Aoki, H. Ueno, and K. Suzuki
Synergistic effect of sphingosine 1-phosphate on thrombin-induced tissue factor expression in endothelial cells
Blood,
September 1, 2003;
102(5):
1693 - 1700.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. I. Kim, E. J. Jo, H.-Y. Lee, M. S. Cha, J. K. Min, C. H. Choi, Y. M. Lee, Y.-A. Choi, S.-H. Baek, S. H. Ryu, et al.
Sphingosine 1-Phosphate in Amniotic Fluid Modulates Cyclooxygenase-2 Expression in Human Amnion-derived WISH Cells
J. Biol. Chem.,
August 22, 2003;
278(34):
31731 - 31736.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Jin, E. Knudsen, L. Wang, Y. Bryceson, B. Damaj, S. Gessani, and A. A. Maghazachi
Sphingosine 1-phosphate is a novel inhibitor of T-cell proliferation
Blood,
June 15, 2003;
101(12):
4909 - 4915.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Carton, D. J. Uhlinger, A. D. Batheja, C. Derian, G. Ho, D. Argenteri, and M. R. D'Andrea
Enhanced Serine Palmitoyltransferase Expression in Proliferating Fibroblasts, Transformed Cell Lines, and Human Tumors
J. Histochem. Cytochem.,
June 1, 2003;
51(6):
715 - 726.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D.-S. Kim, E.-S. Hwang, J.-E. Lee, S.-Y. Kim, S.-B. Kwon, and K.-C. Park
Sphingosine-1-phosphate decreases melanin synthesis via sustained ERK activation and subsequent MITF degradation
J. Cell Sci.,
May 1, 2003;
116(9):
1699 - 1706.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Graeler, G. Shankar, and E. J. Goetzl
Cutting Edge: Suppression of T Cell Chemotaxis by Sphingosine 1-Phosphate
J. Immunol.,
October 15, 2002;
169(8):
4084 - 4087.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Vaidehi, W. B. Floriano, R. Trabanino, S. E. Hall, P. Freddolino, E. J. Choi, G. Zamanakos, and W. A. Goddard III
Prediction of structure and function of G protein-coupled receptors
PNAS,
October 1, 2002;
99(20):
12622 - 12627.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Baudhuin, K. L. Cristina, J. Lu, and Y. Xu
Akt Activation Induced by Lysophosphatidic Acid and Sphingosine-1-phosphate Requires Both Mitogen-Activated Protein Kinase Kinase and p38 Mitogen-Activated Protein Kinase and Is Cell-Line Specific
Mol. Pharmacol.,
September 1, 2002;
62(3):
660 - 671.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Cummings, N. L. Parinandi, A. Zaiman, L. Wang, P. V. Usatyuk, J. G. N. Garcia, and V. Natarajan
Phospholipase D Activation by Sphingosine 1-Phosphate Regulates Interleukin-8 Secretion in Human Bronchial Epithelial Cells
J. Biol. Chem.,
August 9, 2002;
277(33):
30227 - 30235.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Spiegel and S. Milstien
Sphingosine 1-Phosphate, a Key Cell Signaling Molecule
J. Biol. Chem.,
July 12, 2002;
277(29):
25851 - 25854.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chun, E. J. Goetzl, T. Hla, Y. Igarashi, K. R. Lynch, W. Moolenaar, S. Pyne, and G. Tigyi
International Union of Pharmacology. XXXIV. Lysophospholipid Receptor Nomenclature
Pharmacol. Rev.,
June 1, 2002;
54(2):
265 - 269.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. E. Heise, W. L. Santos, A. M. Schreihofer, B. H. Heasley, Y. V. Mukhin, T. L. Macdonald, and K. R. Lynch
Activity of 2-Substituted Lysophosphatidic Acid (LPA) Analogs at LPA Receptors: Discovery of a LPA1/LPA3 Receptor Antagonist
Mol. Pharmacol.,
December 1, 2001;
60(6):
1173 - 1180.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hla, M.-J. Lee, N. Ancellin, J. H. Paik, and M. J. Kluk
Lysophospholipids--Receptor Revelations
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]
|
|
|
|
|
|
|
D. English, J. G.N. Garcia, and D.N. Brindley
Platelet-released phospholipids link haemostasis and angiogenesis
Cardiovasc Res,
February 16, 2001;
49(3):
588 - 599.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Parrill, D.-a. Wang, D. L. Bautista, J. R. Van Brocklyn, Z. Lorincz, D. J. Fischer, D. L. Baker, K. Liliom, S. Spiegel, and G. Tigyi
Identification of Edg1 Receptor Residues That Recognize Sphingosine 1-Phosphate
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]
|
|
|
|
|
|
|
J. H. Paik, S.-s. Chae, M.-J. Lee, S. Thangada, and T. Hla
Sphingosine 1-Phosphate-induced Endothelial Cell Migration Requires the Expression of EDG-1 and EDG-3 Receptors and Rho-dependent Activation of alpha vbeta 3- and beta 1-containing Integrins
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
Sphingosine 1-Phosphate Activates Nuclear Factor-kappa B through Edg Receptors. ACTIVATION THROUGH Edg-3 AND Edg-5, BUT NOT Edg-1, IN HUMAN EMBRYONIC KIDNEY 293 CELLS
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
A Single Amino Acid Determines Lysophospholipid Specificity of the S1P1 (EDG1) and LPA1 (EDG2) Phospholipid Growth Factor Receptors
J. Biol. Chem.,
December 21, 2001;
276(52):
49213 - 49220.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
