Lysophospholipid (S1P) receptors: Introduction

Sphingosine 1-phosphate (S1P) receptors (nomenclature as agreed by NC-IUPHAR Subcommittee on Lysophospholipid receptors [1];) including gene names used by NC-IUPHAR, which are in concert with Human Genome Organization (HUGO), Gene Nomenclature Committee (HGNC), and Mouse Genome Informatics (MGI) nomenclatures. S1P receptors are activated by the endogenous phospholipid derivative sphingosine 1-phosphate (S1P) and at lower apparent affinity by sphingosyl phosphorylcholine (SPC). Originally identified as members of the endothelial differentiation gene (edg) family along with lysophosphatidic acid receptors, the gene names are now designated as S1PR1, etc. to reflect the receptor function of these proteins. S1P has also been described to act at intracellular sites [4], although most cellular phenomena ascribed to S1P can be explained by receptor-mediated mechanisms, with the intracellular functions awaiting further confirmation. The relationship between recombinant and endogenously expressed receptors is unclear. Radioligand binding has been conducted in heterologous expression systems using [32P]S1P (e.g [3]). In native systems, analysis of binding data is complicated by metabolism and high levels of nonspecific binding. Targeted deletion of several S1P receptors and key enzymes involved in S1P biosynthesis or degradation has clarified signalling pathways and physiological roles. Other receptors that appear in the older literature as SPC (or LPC) receptors – G2A, TDAG8, OGR1 and GPR4 – are not receptors for S1P, SPC or LPC, based on current knowledge. A S1P1-T4 fusion protein structure bound to an antagonist in the absence of G proteins has been published [2].

The International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid Receptor Nomenclature Review article [1] provides a useful general overview on the nomenclature and some introductory notes on the pharmacological characteristics of the lysophospholipid family of receptors.


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1. Chun J, Hla T, Lynch KR, Spiegel S, Moolenaar WH. (2010) International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid receptor nomenclature. Pharmacol. Rev., 62 (4): 579-87. [PMID:21079037]

2. Hanson MA, Roth CB, Jo E, Griffith MT, Scott FL, Reinhart G, Desale H, Clemons B, Cahalan SM, Schuerer SC et al.. (2012) Crystal structure of a lipid G protein-coupled receptor. Science, 335 (6070): 851-5. [PMID:22344443]

3. Okamoto H, Takuwa N, Gonda K, Okazaki H, Chang K, Yatomi Y, Shigematsu H, Takuwa Y. (1998) EDG1 is a functional sphingosine-1-phosphate receptor that is linked via a Gi/o to multiple signaling pathways, including phospholipase C activation, Ca2+ mobilization, Ras-mitogen-activated protein kinase activation, and adenylate cyclase inhibition. J. Biol. Chem., 273 (42): 27104-10. [PMID:9765227]

4. Takabe K, Paugh SW, Milstien S, Spiegel S. (2008) "Inside-out" signaling of sphingosine-1-phosphate: therapeutic targets. Pharmacol. Rev., 60 (2): 181-95. [PMID:18552276]

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