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J Biol Chem, Vol. 274, Issue 8, 4626-4632, February 19, 1999
, and
From the Department of Biochemistry and Molecular Biology,
Georgetown University Medical Center, Washington, D. C. 20007 and
the Sphingosine 1-phosphate (SPP) is a lipid second
messenger that also acts as a first messenger through the G
protein-coupled receptor Edg-1. Here we show that SPP also binds to the
related receptors H218 and Edg-3 with high affinity and specificity.
SPP and sphinganine 1-phosphate bind to these receptors, whereas
neither sphingosylphosphorylcholine nor lysophosphatidic acid compete with SPP for binding to either receptor. Transfection of HEK293 cells
with H218 or edg-3, but not edg-1,
induces rounded cell morphology in the presence of serum, which
contains high levels of SPP. SPP treatment of cells overexpressing H218
cultured in delipidated serum causes cell rounding. A similar but less
dramatic effect was observed in cells overexpressing Edg-3 but not with Edg-1. Cell rounding was correlated with apoptotic cell death, probably
as a result of loss of attachment. Nerve growth factor-induced neuritogenesis in PC12 cells was inhibited by overexpression of H218
and to a lesser extent Edg-3. SPP treatment rapidly enhanced neurite
retraction in PC12 cells overexpressing Edg-1, Edg-3, or H218. Thus,
H218, and possibly Edg-3, may be the cell surface receptors responsible
for cell rounding and neurite retraction induced by SPP. Moreover, the
identification of these two additional SPP receptors indicates that a
family of highly specific receptors exists that mediate different
responses to SPP.
Fakultät für Chemie, University of
Konstanz, D-78457 Konstanz, Germany
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S. Mitsutake, M. Tani, N. Okino, K. Mori, S. Ichinose, A. Omori, H. Iida, T. Nakamura, and M. Ito Purification, Characterization, Molecular Cloning, and Subcellular Distribution of Neutral Ceramidase of Rat Kidney J. Biol. Chem., July 6, 2001; 276(28): 26249 - 26259. [Abstract] [Full Text] [PDF]
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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]
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S. M. Mandala, R. Thornton, I. Galve-Roperh, S. Poulton, C. Peterson, A. Olivera, J. Bergstrom, M. B. Kurtz, and S. Spiegel Molecular cloning and characterization of a lipid phosphohydrolase that degrades sphingosine-1- phosphate and induces cell death PNAS, July 5, 2000; 97(14): 7859 - 7864. [Abstract] [Full Text] [PDF]
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