Sphingosine 1-Phosphate Receptor 1 Signaling in Mammalian Cells

The bioactive lipid, sphingosine 1-phosphate (S1P) binds to a family of G protein-coupled receptors, termed S1P(1)-S1P(5). These receptors function in, for example, the cardiovascular system to regulate vascular barrier integrity and tone, the nervous system to regulate neuronal differentiation, myelination and oligodendrocyte/ glial cell survival and the immune system to regulate T-and B-cell subsets and trafficking. S1P receptors also participate in the pathophysiology of autoimmunity, inflammatory disease, cancer, neurodegeneration and others. In this review, we describe how S1P(1) can form a complex with G-protein and beta-arrestin, which function together to regulate effector pathways. We also discuss the role of the S1P(1)-Platelet derived growth factor receptor beta functional complex (which deploys G-protein/ beta-arrestin and receptor tyrosine kinase signaling) in regulating cell migration. Possible mechanisms by which different S1P-chaperones, such as Apolipoprotein M-High-Density Lipoprotein induce biological programmes in cells are also described. Finally, the role of S1P(1) in health and disease and as a target for clinical intervention is appraised.