Sphingosine 1-phosphate receptor 1 signaling in mammalian cells

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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.
Original languageEnglish
Article number344
Pages (from-to)1-18
Number of pages18
Issue number3
Publication statusPublished - 23 Feb 2017


  • sphingosine 1-phosphate
  • G-protein coupled receptor
  • megaplex
  • receptor tyrosine kinase
  • immune trafficking
  • neovascularisation
  • cardiovascular;
  • cancer


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