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

Pyne, Susan and Adams, David R and Pyne, Nigel J. (2016) Sphingosine 1-phosphate and sphingosine kinases in health and disease : recent advances. Progress in Lipid Research, 62. pp. 93-106. ISSN 0163-7827

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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.

    ORCID iDs

    Pyne, Susan ORCID logoORCID: https://orcid.org/0000-0002-6608-9584, Adams, David R and Pyne, Nigel J. ORCID logoORCID: https://orcid.org/0000-0002-5657-4578;
    • Item type:Article
      ID code:55833
      Dates:
      Date
      Event
      1 April 2016
      Published
      10 March 2016
      Published Online
      8 March 2016
      Accepted
      Keywords:Sphingosine 1-phosphate, sphingosine kinase, S1P receptors, intracellular signalling, sphingosine kinase inhibitors, Therapeutics. Pharmacology, Pharmacology, Toxicology and Pharmaceutics(all), SDG 3 - Good Health and Well-being
      Subjects:Medicine > Therapeutics. Pharmacology
      Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
      Depositing user: Pure Administrator
      Date deposited:10 Mar 2016 13:44
      Last modified:23 Sep 2021 05:32
      Related URLs:
      URI:https://strathprints.strath.ac.uk/id/eprint/55833
    CORE (COnnecting REpositories)