Sphingosine 1-phosphate receptors

Brinkmann V, Cyster JG, Hla T (2004) FTY720 sphingosine 1-phosphate receptor-1 in the control of lymphocyte egress and endothelial barrier function. Am J Transplant 4 1019-1025... 

Most GPCRs interact with and activate more than one G-protein subfamily, e.g., with Gs plus Gq/n (histamine H2, parathyroid hormone and calcitonin recqrtors), Gs plus G (luteinising hormone receptor, 32-adrenoceptor) or Gq/11 plus G12/13 (thromboxane A2, angiotensin ATb endothelin ETA receptors). Some receptors show even broader G-protein coupling, e.g., to Gi, Gq/n plus Gi n ( protease-activated receptors, lysophosphatidate and sphingosine-1-phosphate receptors) or even to all four G-protein subfamilies (thyrotropin receptor). This multiple coupling results in multiple signaling via different pathways and in a concerted reaction of the cell to the stimulus. 

Chemokine and Sphingosine-1-phosphate Receptors in Tissue-Specific... 

Allende ML, Dreier JL, Mandala S, Proia RL. Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration. J Biol Chem 2004 279 15396-401. 

Cinamon G, Matloubian M, Lesneski MJ, et al. Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone. Nat Immunol 2004 5 713-720. 

An, S., Bleu, T. and Zheng, Y., 1999, Transduction of intracellular calcium signals through G protein- mediated activation ofphosphohpase C by recombinant sphingosine 1- phosphate receptors. Mol. Pharmacol. 55 787-794. 

Sillard, R., Harii, K. and Takuwa, Y., 1999, The novel sphingosine 1-phosphate receptor AGR16 is coupled via pertussis toxin-sensitive and -insensitive G-proteins to multiple signaling pathways. Biochem. J. 337 67-75. 

Hobson, J.P., Rosenfeldt, H.M., Barak, L.S., Olivera, A., Poulton, S., Caron, M., Milstien, S. and Spiegel, S., 2001, Role of sphingosine 1-phosphate receptor EDGl in PDGF-induced cell motility. Science 291 1800-1803. 

Characterization of a novel sphingosine 1-phosphate receptor, EDG8,/. Biol. Chem. 275 14281-14286. 

Ishizuka, T., Murata, N., Kanda, T., Kobayashi, I., Ohta, H., Ui, M. and Okajima, F., 1999, Comparison of intrinsic activities of the putative sphingosine 1-phosphate receptor sub-types to regulate several signaling pathways in their cDNA-transfected Chinese hamster ovary cells. J. Biol. Chem. 274 23940-23947. 

Chiba, K. 2005. FTY720, a new class of immunomodulator, inhibits lymphocyte egress from secondary lymphoid tissues and thymus by antagonistic activity at sphingosine 1-phosphate receptors. Pharmacology and Therapeutics, 108 308-319. 

The major classes of immunosuppressive drugs employed in clinical practice to avoid tissue rejection include calcineurin inhibitors, target of rapamycin (TOR) inhibitors, sphingosine-1 -phosphate receptor (S1P-R) modulators, cytotoxic agents, glucocorticoids and monoclonal antibodies. These drugs need to be used on a lifelong basis and have major undesirable side effects. 

Brinkmann, V. (2007). Sphingosine 1-phosphate receptors in health and disease Mechanistic insights from gene deletion studies and reverse pharmacology. Pharmacol. Ther. 115(1), 84-105. 

Im, D. S., Clemens, J., Macdonald, T. L., and Lynch, K. R. (2001). Characterization of the human and mouse sphingosine 1-phosphate receptor, S1P5 (Edg-8) Structure-activity relationship of sphingosinel-phosphate receptors. Biochemistry 40(46), 14053-14060. 

Sphingosine-1-phosphate receptors EDG-1 and EDG-3 bind SIP generated from phosphorylation of sphingosine by sphingosine kinase. The binding of SIP and sphinganine 1-phosphate (dihydrosphingosine 1-phosphate) to EDG-1 promotes chemotaxis via a Gai-mediated mechanism. 

Hla T. Sphingosine 1-phosphate receptors. Prostaglandins Other Lipid Mediat. 2001 64 135-142. 

Kono M, Mi Y, Liu Y, Sasaki T, Allende ML, Wu YP, Yamashita T, Proia RL. The sphingosine-1-phosphate receptors SlPl, S1P2, and S1P3 function coordinately during embryonic angiogenesis. J. Biol. Chem. 2004 279 29367-29373. 

Billy E, Theuer A, Hla T, Wood J. Antagonism of sphingosine-1-phosphate receptors by FTY720 inhibits angiogenesis and tumor 194. vascularization. Cancer Res. 2006 66 221-231. 

Sphingosine-1-phosphate receptor modulators FTY720 (Fingolimod)... 

Ancellin N, Hla T (1999) Differential pharmacological properties and signal transduction of the sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5. J Biol Chem 274 18997-19002... 

Brinkmann V, Davis MD, Heise CE, Albert R, Cottens S, Hof R, Bruns C, Prieschl E. Baumruker T, Hies-tand P, Foster CA, Zolhnger M, Lynch KR (2002) The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem 277 21453 57... 

Graeler M, Goetzl EJ (2002) Activation-regulated expression and chemotactic function of sphingosine 1-phosphate receptors in mouse splenic T cells. FASEB J 16 1874-1878... 

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