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Molecules 2017, 22(3), 344; doi:10.3390/molecules22030344

Sphingosine 1-Phosphate Receptor 1 Signaling in Mammalian Cells

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK
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Academic Editor: Yung Hou Wong
Received: 22 January 2017 / Revised: 15 February 2017 / Accepted: 18 February 2017 / Published: 23 February 2017
(This article belongs to the Special Issue G-protein Coupled Receptor Structure and Function)
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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. View Full-Text
Keywords: sphingosine 1-phosphate; sphingosine 1-phosphate receptor 1; G-protein coupled receptor megaplex; receptor tyrosine kinase; immune trafficking; neovascularisation; cardiovascular; cancer sphingosine 1-phosphate; sphingosine 1-phosphate receptor 1; G-protein coupled receptor megaplex; receptor tyrosine kinase; immune trafficking; neovascularisation; cardiovascular; cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Pyne, N.J.; Pyne, S. Sphingosine 1-Phosphate Receptor 1 Signaling in Mammalian Cells. Molecules 2017, 22, 344.

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