Lysophospholipid (S1P) receptors: Introduction

Sphingosine 1-phosphate (S1P) receptors (nomenclature as agreed by NC-IUPHAR Subcommittee on Lysophospholipid receptors [2];) are activated by the endogenous lipid, sphingosine 1-phosphate (S1P). Originally cloned as orphan members of the endothelial differentiation gene (edg) family [1,4], the receptors are currently designated as S1P1 through S1P5 to reflect the receptor function of these proteins. S1P has also been described to act at intracellular sites [6], 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 [5]). 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 [3].

The International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid Receptor Nomenclature Review article [2] provides a useful general overview on the nomenclature and some introductory notes on the pharmacological characteristics of the lysophospholipid family of receptors.


Show »

1. Blaho VA. (2020) Druggable Sphingolipid Pathways: Experimental Models and Clinical Opportunities. Adv Exp Med Biol, 1274: 101-135. [PMID:32894509]

2. 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]

3. 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]

4. Mizuno H, Kihara Y. (2020) Druggable Lipid GPCRs: Past, Present, and Prospects. Adv Exp Med Biol, 1274: 223-258. [PMID:32894513]

5. 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]

6. 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]

How to cite this page

To cite this family introduction, please use the following:

Database page citation (select format):