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Gene Review

S1PR2  -  sphingosine-1-phosphate receptor 2

Homo sapiens

Synonyms: AGR16, EDG-5, EDG5, Endothelial differentiation G-protein coupled receptor 5, Gpcr13, ...
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Disease relevance of EDG5


High impact information on EDG5

  • S1P induced comparable increases in the amounts of GTP-RhoA in EDG3 and EDG5 cells [6].
  • Actin staining of S1P stimulated U118 cells overexpressing beta-galactosidase resulted in pronounced stress fiber formation that was exacerbated by S1P2 overexpression, partially blocked by S1P1, or totally abolished by pretreatment with Y-27632 [7].
  • S1P-mediated inhibition correlated with S1P2 receptor expression [7].
  • FTY720-P, an S1P analogue that binds all S1P receptors except S1P2, did not inhibit glioblastoma cell migration [7].
  • Our data also indicated that Edg3 and Edg5 mediated the serum response element activation through transcriptional factors Elk-1 and serum response factor [2].

Biological context of EDG5

  • Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5 [2].
  • 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 [8].
  • Northern analysis revealed that brain H218 mRNA is preferentially expressed during embryogenesis [9].
  • No individuals with the S1P2 haplotype were observed due to an extreme linkage disequilibrium between the two RFLP loci [10].
  • Chromosomal mapping employing a rat somatic cell readiation hybrid panel demonstrated that nrg-1 is linked to marker D8Rat54 and tightly associated with H218 on chromosome 8 [11].

Anatomical context of EDG5

  • Consistent with angiogenesis in general during decidualization, we believe EDG1 and EDG5 to be regulated by the embryo because no microvascular expression for these receptors was observed in oil-induced deciduomas [12].
  • Unlike EDG3 and EDG5, which are expressed in the smooth muscle cell layer of the human aorta, no signal corresponding to EDG1 expression could be detected in the aorta [13].
  • Nerve growth factor-induced neuritogenesis in PC12 cells was inhibited by overexpression of H218 and to a lesser extent Edg-3 [8].
  • Thus, H218, and possibly Edg-3, may be the cell surface receptors responsible for cell rounding and neurite retraction induced by SPP [8].
  • We showed that H218 and Edg3 were capable of mediating S1P-induced mobilization of intracellular Ca2+ when transiently transfected in human TAg-Jurkat T cells [4].

Associations of EDG5 with chemical compounds


Analytical, diagnostic and therapeutic context of EDG5


  1. Sphingosine-1-phosphate stimulates human glioma cell proliferation through Gi-coupled receptors: role of ERK MAP kinase and phosphatidylinositol 3-kinase beta. Van Brocklyn, J., Letterle, C., Snyder, P., Prior, T. Cancer Lett. (2002) [Pubmed]
  2. Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5. An, S., Zheng, Y., Bleu, T. J. Biol. Chem. (2000) [Pubmed]
  3. Sphingosine 1-phosphate receptor expression profile in human gastric cancer cells: differential regulation on the migration and proliferation. Yamashita, H., Kitayama, J., Shida, D., Yamaguchi, H., Mori, K., Osada, M., Aoki, S., Yatomi, Y., Takuwa, Y., Nagawa, H. J. Surg. Res. (2006) [Pubmed]
  4. Transduction of intracellular calcium signals through G protein-mediated activation of phospholipase C by recombinant sphingosine 1-phosphate receptors. An, S., Bleu, T., Zheng, Y. Mol. Pharmacol. (1999) [Pubmed]
  5. Sphingosine kinase-1 expression correlates with poor survival of patients with glioblastoma multiforme: roles of sphingosine kinase isoforms in growth of glioblastoma cell lines. Van Brocklyn, J.R., Jackson, C.A., Pearl, D.K., Kotur, M.S., Snyder, P.J., Prior, T.W. J. Neuropathol. Exp. Neurol. (2005) [Pubmed]
  6. Inhibitory regulation of Rac activation, membrane ruffling, and cell migration by the G protein-coupled sphingosine-1-phosphate receptor EDG5 but not EDG1 or EDG3. Okamoto, H., Takuwa, N., Yokomizo, T., Sugimoto, N., Sakurada, S., Shigematsu, H., Takuwa, Y. Mol. Cell. Biol. (2000) [Pubmed]
  7. The G protein-coupled receptor S1P2 regulates Rho/Rho kinase pathway to inhibit tumor cell migration. Lepley, D., Paik, J.H., Hla, T., Ferrer, F. Cancer Res. (2005) [Pubmed]
  8. Sphingosine 1-phosphate-induced cell rounding and neurite retraction are mediated by the G protein-coupled receptor H218. Van Brocklyn, J.R., Tu, Z., Edsall, L.C., Schmidt, R.R., Spiegel, S. J. Biol. Chem. (1999) [Pubmed]
  9. Cloning and characterization of a putative G-protein coupled receptor potentially involved in development. MacLennan, A.J., Browe, C.S., Gaskin, A.A., Lado, D.C., Shaw, G. Mol. Cell. Neurosci. (1994) [Pubmed]
  10. Restriction fragment length polymorphisms of the human N-myc gene: relationship to gene amplification. Kurosawa, H., Yamada, M., Nakagome, Y. Oncogene (1987) [Pubmed]
  11. Molecular cloning, tissue-specific expression, and chromosomal localization of a novel nerve growth factor-regulated G-protein- coupled receptor, nrg-1. Glickman, M., Malek, R.L., Kwitek-Black, A.E., Jacob, H.J., Lee, N.H. Mol. Cell. Neurosci. (1999) [Pubmed]
  12. Sphingosine-1-phosphate receptor expression and signaling correlate with uterine prostaglandin-endoperoxide synthase 2 expression and angiogenesis during early pregnancy. Skaznik-Wikiel, M.E., Kaneko-Tarui, T., Kashiwagi, A., Pru, J.K. Biol. Reprod. (2006) [Pubmed]
  13. Cell type-specific localization of human cardiac S1P receptors. Mazurais, D., Robert, P., Gout, B., Berrebi-Bertrand, I., Laville, M.P., Calmels, T. J. Histochem. Cytochem. (2002) [Pubmed]
  14. EDG3 is a functional receptor specific for sphingosine 1-phosphate and sphingosylphosphorylcholine with signaling characteristics distinct from EDG1 and AGR16. Okamoto, H., Takuwa, N., Yatomi, Y., Gonda, K., Shigematsu, H., Takuwa, Y. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  15. Sphingosine-1-phosphate inhibits motility of human breast cancer cells independently of cell surface receptors. Wang, F., Van Brocklyn, J.R., Edsall, L., Nava, V.E., Spiegel, S. Cancer Res. (1999) [Pubmed]
  16. Sphingosine 1-phosphate evokes calcium signals in C2C12 myoblasts via Edg3 and Edg5 receptors. Meacci, E., Cencetti, F., Formigli, L., Squecco, R., Donati, C., Tiribilli, B., Quercioli, F., Zecchi Orlandini, S., Francini, F., Bruni, P. Biochem. J. (2002) [Pubmed]
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