Sphingosine kinases : emerging structure function insights

Adams, David R. and Pyne, Susan and Pyne, Nigel J. (2016) Sphingosine kinases : emerging structure function insights. Trends in Biochemical Sciences, 41 (5). pp. 395-409. ISSN 0968-0004

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    Abstract

    Sphingosine kinases (SK1 and SK2) catalyse the conversion of sphingosine into sphingosine 1-phosphate and control fundamental cellular processes, including cell survival, proliferation, differentiation, migration, and immune function. In this review, we highlight recent breakthroughs in the structural and functional characterisation of SK1 and these are contextualised by analysis of crystal structures for closely related prokaryotic lipid kinases. We identify a putative dimerisation interface and propose novel regulatory mechanisms governing structural plasticity induced by phosphorylation and interaction with phospholipids and proteins. Our analysis suggests that the catalytic function and regulation of the enzymes might be dependent on conformational mobility and it provides a roadmap for future interrogation of SK1 function and its role in physiology and disease.

    Author(s):Adams, David R., Pyne, Susan ORCID logoORCID: https://orcid.org/0000-0002-6608-9584 and Pyne, Nigel J. ORCID logoORCID: https://orcid.org/0000-0002-5657-4578
    Item type:Article
    ID code:55993
    Keywords:sphingosine kinase, SK1, SK2, diacylglycerol kinase, membrane curvature, TRAF2, Pharmacy and materia medica, Neoplasms. Tumors. Oncology (including Cancer), Biochemistry, Molecular Biology
    Subjects:Medicine > Pharmacy and materia medica
    Medicine > Internal medicine > Neoplasms. Tumors. Oncology (including Cancer)
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:23 Mar 2016 16:57
    Last modified:19 Jan 2020 12:28
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/55993
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