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Sphingosine-1-phosphate and its receptors: Structure, signaling, and influence

Academic Article
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Overview

authors

  • Rosen, Hugh
  • Stevens, Raymond
  • Hanson, Michael
  • Roberts, Edward
  • Oldstone, Michael

publication date

  • 2013

journal

  • Annual Review of Biochemistry  Journal

abstract

  • The sphingosine-1-phosphate (S1P) receptor signaling system has biological and medical importance and is the first lipid G protein-coupled receptor (GPCR) structure to be solved to 2.8-Å resolution. S1P binds to five high-affinity GPCRs generating multiple downstream signals that play essential roles in vascular development and endothelial integrity, control of cardiac rhythm, and routine oral treatment of multiple sclerosis. Genetics, chemistry, and now structural biology have advanced this integrated biochemical system. The S1P receptors have a novel N-terminal fold that occludes access to the binding pocket from the extracellular environment as well as orthosteric and bitopic ligands with very different physicochemical properties. S1P receptors and metabolizing enzymes have been deleted, inducibly deleted, and knocked in as tagged or altered receptors in mice. An array of genetic models allows analysis of integrated receptor function in vivo. We can now directly understand causal relationships among protein expression, signal, and control points in physiology and pathology.

subject areas

  • Animals
  • Ligands
  • Mice
  • Receptors, G-Protein-Coupled
  • Receptors, Lysosphingolipid
  • Signal Transduction
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Research

keywords

  • GPCR
  • chemical biology
  • receptor crystal structure
  • sphingosine-1-phosphate
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Identity

International Standard Serial Number (ISSN)

  • 0066-4154 978-0-8243-0882-7

Digital Object Identifier (DOI)

  • 10.1146/annurev-biochem-062411-130916

PubMed ID

  • 23527695
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Additional Document Info

start page

  • 637

end page

  • 662

volume

  • 82

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