Sphingosine 1-phosphate and sphingosine kinases in health and disease: recent advances

Susan Pyne, David R Adams, Nigel J. Pyne

Research output: Contribution to journalLiterature review

57 Citations (Scopus)

Abstract

Sphingosine kinases (isoforms SK1 and SK2) catalyse the formation of a bioactive lipid, sphingosine 1-phosphate (S1P). S1P is a well-established ligand of a family of five S1P-specific G protein coupled receptors but also has intracellular signaling roles. There is substantial evidence to support a role for sphingosine kinases and S1P in health and disease. This review summarises recent advances in the area in relation to receptor-mediated signaling by S1P and novel intracellular targets of this lipid. New evidence for a role of each sphingosine kinase isoform in cancer, the cardiovascular system, central nervous system, inflammation and diabetes is discussed. There is continued research to develop isoform selective SK inhibitors, summarised here. Analysis of the crystal structure of SK1 with the SK1-selective inhibitor, PF-543, is used to identify residues that could be exploited to improve selectivity in SK inhibitor development for future therapeutic application.
LanguageEnglish
Pages93-106
Number of pages14
JournalProgress in Lipid Research
Volume62
Early online date10 Mar 2016
DOIs
Publication statusPublished - 1 Apr 2016

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Health
Protein Isoforms
Lipids
Cardiovascular system
Neurology
Medical problems
G-Protein-Coupled Receptors
Cardiovascular System
Central Nervous System
Crystal structure
sphingosine 1-phosphate
sphingosine kinase
Ligands
Inflammation
Research
Neoplasms
Therapeutics

Keywords

  • Sphingosine 1-phosphate
  • sphingosine kinase
  • S1P receptors
  • intracellular signalling
  • sphingosine kinase inhibitors

Cite this

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abstract = "Sphingosine kinases (isoforms SK1 and SK2) catalyse the formation of a bioactive lipid, sphingosine 1-phosphate (S1P). S1P is a well-established ligand of a family of five S1P-specific G protein coupled receptors but also has intracellular signaling roles. There is substantial evidence to support a role for sphingosine kinases and S1P in health and disease. This review summarises recent advances in the area in relation to receptor-mediated signaling by S1P and novel intracellular targets of this lipid. New evidence for a role of each sphingosine kinase isoform in cancer, the cardiovascular system, central nervous system, inflammation and diabetes is discussed. There is continued research to develop isoform selective SK inhibitors, summarised here. Analysis of the crystal structure of SK1 with the SK1-selective inhibitor, PF-543, is used to identify residues that could be exploited to improve selectivity in SK inhibitor development for future therapeutic application.",
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Sphingosine 1-phosphate and sphingosine kinases in health and disease : recent advances. / Pyne, Susan; Adams, David R; Pyne, Nigel J.

In: Progress in Lipid Research, Vol. 62, 01.04.2016, p. 93-106.

Research output: Contribution to journalLiterature review

TY - JOUR

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T2 - Progress in Lipid Research

AU - Pyne, Susan

AU - Adams, David R

AU - Pyne, Nigel J.

PY - 2016/4/1

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N2 - Sphingosine kinases (isoforms SK1 and SK2) catalyse the formation of a bioactive lipid, sphingosine 1-phosphate (S1P). S1P is a well-established ligand of a family of five S1P-specific G protein coupled receptors but also has intracellular signaling roles. There is substantial evidence to support a role for sphingosine kinases and S1P in health and disease. This review summarises recent advances in the area in relation to receptor-mediated signaling by S1P and novel intracellular targets of this lipid. New evidence for a role of each sphingosine kinase isoform in cancer, the cardiovascular system, central nervous system, inflammation and diabetes is discussed. There is continued research to develop isoform selective SK inhibitors, summarised here. Analysis of the crystal structure of SK1 with the SK1-selective inhibitor, PF-543, is used to identify residues that could be exploited to improve selectivity in SK inhibitor development for future therapeutic application.

AB - Sphingosine kinases (isoforms SK1 and SK2) catalyse the formation of a bioactive lipid, sphingosine 1-phosphate (S1P). S1P is a well-established ligand of a family of five S1P-specific G protein coupled receptors but also has intracellular signaling roles. There is substantial evidence to support a role for sphingosine kinases and S1P in health and disease. This review summarises recent advances in the area in relation to receptor-mediated signaling by S1P and novel intracellular targets of this lipid. New evidence for a role of each sphingosine kinase isoform in cancer, the cardiovascular system, central nervous system, inflammation and diabetes is discussed. There is continued research to develop isoform selective SK inhibitors, summarised here. Analysis of the crystal structure of SK1 with the SK1-selective inhibitor, PF-543, is used to identify residues that could be exploited to improve selectivity in SK inhibitor development for future therapeutic application.

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