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.
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 language | English |
|---|---|
| Pages (from-to) | 395-409 |
| Number of pages | 15 |
| Journal | Trends in Biochemical Sciences |
| Volume | 41 |
| Issue number | 5 |
| Early online date | 25 Mar 2016 |
| DOIs | |
| Publication status | Published - 1 May 2016 |
Keywords
- sphingosine kinase
- SK1
- SK2
- diacylglycerol kinase
- membrane curvature
- TRAF2
