TABLE 1.

List the various S1P receptors, tissue expression, and physiological functions

Receptors	G protein Coupling	Tissue Expression	Signaling Pathways	Physiological Functions	Reference
S1PR1	Gαi/o	Ubiquitously expressed, high in CD19+ B cells and cerebellum.	Protein kinase AKT and the small GTPase Rac, MAPK, activates NF-κB, STAT3.	Trafficking of lymphocytes and hematopoietic cells including T and B lymphocytes, NKT cells, dendritic cells, macrophages, neutrophils, hematopoietic progenitors, mast cells, and osteoclasts in both homeostatic and disease settings. Vascular development and integrity, promoting metastasis.	(26, 55–60)
S1PR2	Gi, Gq, Gα12/13	Ubiquitously expressed, immune cells (dendritic cells, macrophages, eosinophils, mast cells, NKT) Smooth muscle cells, cardiomyocytes, hepatocytes, cholangiocytes, gut epithelial cells.	GTPase Rho activation, Rho-dependent Rac inhibition and 3′-specific phosphoinositide phosphatase (PTEN) stimulation, NF-κB activation.	Inhibits cell motility through inhibition of Rac, involved in cell proliferation, motility and transcriptional activation, heart development, vascular development, role in atherosclerosis, bone maintenance, muscle regeneration, B cell function, promoting metastasis, hepatic lipid metabolism and gene expression.	(9, 11, 55, 56, 59, 61)
S1PR3	Gαi/o, Gαq, and Gα12/13	Highest expression in heart, lung, spleen, kidney, intestine, diaphragm; immune cells (dendritic cells, eosinophils, lymphocytes B) endothelial cells smooth muscle cells, cardiomyocytes neuronal cells (astrocytes, oligodendrocytes).	Leading to the generation of inositol trisphosphate and diacylglycerol with subsequent calcium mobilization and activation of PKC pathways respectively.	Cell motility, ER+ breast cancer progression, regulates endothelial barrier function, involved in sepsis, regulation of heart rate, regulation of vascular tone (relaxation) survival in ischemia-reperfusion cardiomyocytes.	(55, 56, 58, 59)
S1PR4	GαI, Gα12/13	Primarily expressed in lymphoid tissues and blood cells, especially CD19+ B cells, dendritic cells, T cells, NKT cells and lung	Preferentially activates phospholipase C/IP3/Ca2+, MAPK, and Rho.	Migration of dendritic and neutrophil cells, ER− breast cancer poor prognosis.	(55, 56, 59)
S1PR5	Gi, Gα12/13	Mostly expressed in brain, skin and natural killer cells.	Preferentially activates phospholipase C channels/IP3/Ca2+, PI3K/AKT Rho, and inhibition of adenylate cyclase.	Similar to the role S1PR1, involved in T and B cell trafficking, promotes the egress of NK cells from bone marrow and lymph nodes into blood and other tissues.	(55, 56, 59)