In 1990, S1PR1 was the first member of the S1P receptor family to be cloned from endothelial cells.[1] Later, S1PR2 and S1PR3 were cloned from rat brain and a human genomic library respectively.[2][3] Finally, S1P4 and S1PR5 were cloned from in vitro differentiated human dendritic cells and rat cDNA library.[4][5]
The sphingosine-1-phosphate receptors regulate fundamental biological processes such as cell proliferation, angiogenesis, migration, cytoskeleton organization, endothelial cell chemotaxis, immune cell trafficking and mitogenesis. Sphingosine-1-phosphate receptors are also involved in immune-modulation and directly involved in suppression of innate immune responses from T cells.[6]
Sphingosine-1-phosphate (S1P) receptors are divided into five subtypes: S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5.
They are expressed in a wide variety of tissues, with each subtype exhibiting a different cell specificity, although they are found at their highest density on leukocytes. S1PR1, 2 and 3 receptors are expressed ubiquitously. The expression of S1PR4 and S1PR5 are less widespread. S1PR4 is confined to lymphoid and hematopoietic tissues whereas S1PR5 primarily located in the white matter of the central nervous system (CNS) and spleen.
^Okazaki H, Ishizaka N, Sakurai T, Kurokawa K, Goto K, Kumada M, Takuwa Y (February 1993). "Molecular cloning of a novel putative G protein-coupled receptor expressed in the cardiovascular system". Biochem. Biophys. Res. Commun. 190 (3): 1104–9. doi:10.1006/bbrc.1993.1163. PMID8382486.
^MacLennan AJ, Browe CS, Gaskin AA, Lado DC, Shaw G (June 1994). "Cloning and characterization of a putative G-protein coupled receptor potentially involved in development". Mol. Cell. Neurosci. 5 (3): 201–9. doi:10.1006/mcne.1994.1024. PMID8087418. S2CID34088289.
^Gräler MH, Bernhardt G, Lipp M (October 1998). "EDG6, a novel G-protein-coupled receptor related to receptors for bioactive lysophospholipids, is specifically expressed in lymphoid tissue". Genomics. 53 (2): 164–9. doi:10.1006/geno.1998.5491. PMID9790765.
^Nakamura T, Asano M, Sekiguchi Y, Mizuno Y, Tamaki K, Kimura T, Nara F, Kawase Y, Shimozato T, Doi H, Kagari T, Tomisato W, Inoue R, Nagasaki M, Yuita H, Oguchi-Oshima K, Kaneko R, Watanabe N, Abe Y, Nishi T (February 2012). "Discovery of CS-2100, a potent, orally active and S1P3-sparing S1P1 agonist". Bioorg. Med. Chem. Lett. 22 (4): 1788–92. doi:10.1016/j.bmcl.2011.12.019. PMID22264485.
