Sphingosine Kinases: Emerging Structure-Function Insights

David Roger Adams, Susan Pyne, Nigel J. Pyne

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)395-409
Number of pages15
JournalTrends in Biochemical Sciences
Volume41
Issue number5
Early online date25 Mar 2016
DOIs
Publication statusPublished - May 2016

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