sphingosine-1-phosphate receptor
{{Infobox protein
| Name = Sphingosine-1-phosphate receptor
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The sphingosine-1-phosphate receptors are a class of G protein-coupled receptors that are targets of the lipid signalling molecule Sphingosine-1-phosphate (S1P). They are divided into five subtypes: S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5.
Discovery
In 1990, S1PR1 was the first member of the S1P receptor family to be cloned from endothelial cells.{{cite journal |vauthors=Hla T, Maciag T | title = An abundant transcript induced in differentiating human endothelial cells encodes a polypeptide with structural similarities to G-protein-coupled receptors | journal = J. Biol. Chem. | volume = 265 | issue = 16 | pages = 9308–13 |date=June 1990 | doi = 10.1016/S0021-9258(19)38849-0 | pmid = 2160972 | doi-access = free }} Later, S1PR2 and S1PR3 were cloned from rat brain and a human genomic library respectively.{{cite journal |vauthors=Okazaki H, Ishizaka N, Sakurai T, Kurokawa K, Goto K, Kumada M, Takuwa Y | title = Molecular cloning of a novel putative G protein-coupled receptor expressed in the cardiovascular system | journal = Biochem. Biophys. Res. Commun. | volume = 190 | issue = 3 | pages = 1104–9 |date=February 1993 | pmid = 8382486 | doi = 10.1006/bbrc.1993.1163 }}{{cite journal |vauthors=MacLennan AJ, Browe CS, Gaskin AA, Lado DC, Shaw G | title = Cloning and characterization of a putative G-protein coupled receptor potentially involved in development | journal = Mol. Cell. Neurosci. | volume = 5 | issue = 3 | pages = 201–9 |date=June 1994 | pmid = 8087418 | doi = 10.1006/mcne.1994.1024 | s2cid = 34088289 }} Finally, S1P4 and S1PR5 were cloned from in vitro differentiated human dendritic cells and rat cDNA library.{{cite journal |vauthors=Gräler MH, Bernhardt G, Lipp M | title = EDG6, a novel G-protein-coupled receptor related to receptors for bioactive lysophospholipids, is specifically expressed in lymphoid tissue | journal = Genomics | volume = 53 | issue = 2 | pages = 164–9 |date=October 1998 | pmid = 9790765 | doi = 10.1006/geno.1998.5491 }}{{cite journal |vauthors=Im DS, Heise CE, Ancellin N, O'Dowd BF, Shei GJ, Heavens RP, Rigby MR, Hla T, Mandala S, McAllister G, George SR, Lynch KR | title = Characterization of a novel sphingosine 1-phosphate receptor, Edg-8 | journal = J. Biol. Chem. | volume = 275 | issue = 19 | pages = 14281–6 |date=May 2000 | pmid = 10799507 | doi =10.1074/jbc.275.19.14281 | doi-access = free }}
Function
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.{{cite journal |author=Sharma, N|title=Sphingosine-1-phosphate suppresses TLR-induced CXCL8 secretion from human T cells. |journal=J Leukoc Biol |volume=93|issue=4 |pages=521–528 |year=2013|pmid=23345392 |doi=10.1189/jlb.0712328|display-authors=etal|doi-access=}}
Subtypes
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.
G protein interactions and selective ligands
The sphingosine-1-phosphate (S1P) is the endogenous agonist for the five subtypes.
References
{{Reflist|35em}}
{{G protein-coupled receptors}}
{{Lysophospholipid signaling}}