title: Sphingosine 1-Phosphate Receptor 1 Signaling in Mammalian Cells.
abstract: The bioactive lipid, sphingosine 1-phosphate (S1P) binds to a family of G protein-coupled receptors, termed S1P₁-S1P₅. 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 S1P₁ can form a complex with G-protein and β-arrestin, which function together to regulate effector pathways. We also discuss the role of the S1P₁-Platelet derived growth factor receptor β functional complex (which deploys G-protein/β-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 S1P₁ in health and disease and as a target for clinical intervention is appraised.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. n.j.pyne@strath.ac.uk.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Pyne
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. susan.pyne@strath.ac.uk.
authors.forename: Susan
authors.initials: S
authors.lastname: Pyne
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism*; D001665:Binding Sites; D002465:Cell Movement; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D011485:Protein Binding; D049349:Receptors, Lysosphingolipid / Q000737:chemistry / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D000071557:beta-Arrestins / Q000378:metabolism*
chemical_list: D001053:Apolipoproteins; D049349:Receptors, Lysosphingolipid; D000071557:beta-Arrestins; D017479:Receptors, Platelet-Derived Growth Factor; D019204:GTP-Binding Proteins
keywords: G-protein coupled receptor megaplex; cancer; cardiovascular; immune trafficking; neovascularisation; receptor tyrosine kinase; sphingosine 1-phosphate; sphingosine 1-phosphate receptor 1