Sphingosine 1-Phosphate Receptor 4 Antibodies

The sphingosine-1-phosphate receptor 4 (S1P4 receptor) is a G protein-coupled receptor (GPCR) that mediates the effects of sphingosine-1-phosphate (S1P), a bioactive lipid involved in immune regulation and cell signaling. S1P4 receptor expression is predominantly restricted to lymphoid and hematopoietic tissues, including T cells, dendritic cells, macrophages, and other immune cell populations, where it is regulated by differentiation status and inflammatory stimuli. Upon activation, the receptor primarily couples to Gi and G12/13 proteins, modulating intracellular signaling pathways such as PI3K, MAPK, and Rho GTPase activation. S1P4 signaling contributes to immune cell migration, cytokine production, dendritic cell function, and adaptive immune responses. Receptor activity is further regulated by ligand availability, receptor internalization, and desensitization following prolonged stimulation. Aberrant S1P4 signaling has been implicated in inflammatory disorders, autoimmune diseases, and certain hematological malignancies, although its precise physiological roles remain under investigation. While several experimental S1P4-selective agonists and antagonists have been described, no S1P4-specific drugs have yet been approved for clinical use, and current therapeutic S1P receptor modulators show limited or no activity at this receptor subtype. Loss of S1P4 impairs splenic germinal center response to sepsis and results in abnormal megakaryocyte morphology. S1P4 receptors are regulated by phosphorylation of carboxyl-terminal serine364/serine344/serine368 (pS364/pS366/pS368-S1P4). This nomenclature refers to the human S1P4 receptor. This phosphorylation motif is conserved across species and similar in mice, rats and humans. For more information on S1P4 pharmacology please refer to the IUPHAR database. For further reading refer to:

Chun J, Hla T, Lynch KR, Spiegel S, Moolenaar WH. International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid receptor nomenclature. Pharmacol Rev. 2010 Dec;62(4):579-87. doi: 10.1124/pr.110.003111. PMID: 21079037; PMCID: PMC2993255.

Kihara Y, Maceyka M, Spiegel S, Chun J. Lysophospholipid receptor nomenclature review: IUPHAR Review 8. Br J Pharmacol. 2014 Aug;171(15):3575-94. doi: 10.1111/bph.12678. Epub 2014 Jul 12. PMID: 24602016; PMCID: PMC4128058.

Blaho V, Chun J, Herr D, Jones D, Jonnalagadda D, Kihara Y. Lysophospholipid (S1P) receptors in GtoPdb v.2023.1. IUPHAR/BPS Guide to Pharmacology CITE. 2023; 2023(1).