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A lipid binding domain in sphingosine kinase 2

Academic Article
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Overview

authors

  • Don, A. S.
  • Rosen, Hugh

publication date

  • February 2009

journal

  • Biochemical and Biophysical Research Communications  Journal

abstract

  • The lipid second messenger sphingosine 1-phosphate (S1P) is a critical mediator of cellular proliferation and survival signals, and is essential for vasculogenesis and neurogenesis. S1P formation is catalysed by sphingosine kinases 1 and 2 (Sphk1 and Sphk2). We have found that the endogenous glycolipid sulfatide (3-O-sulfogalactosylceramide) binds to and inhibits the activity of Sphk2 and the closely related ceramide kinase (Cerk), but not Sphk1. Using sulfatide as a probe, we mapped the lipid binding domain to the N-terminus of Sphk2 (residues 1-175), a region of sequence that is absent in Sphk1, but aligns with a pleckstrin homology domain in Cerk. Accordingly, Sphk2 bound to phosphatidylinositol monophosphates but not to abundant cellular phospholipids. Deleting the N-terminal domain reduced Sphk2 membrane localisation in cells. We have therefore identified a lipid binding domain in Sphk2 that is important for the enzyme's sub-cellular localisation.

subject areas

  • Catalytic Domain
  • Cell Line
  • Cell Membrane
  • Humans
  • Phosphatidylinositol Phosphates
  • Phosphotransferases (Alcohol Group Acceptor)
  • Protein Structure, Tertiary
  • Sulfoglycosphingolipids
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Research

keywords

  • Ceramide kinase
  • Pleckstrin homology
  • Sphingosine 1-phosphate
  • Sphingosine kinase
  • Sulfatide
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Identity

PubMed Central ID

  • PMC2657340

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2009.01.075

PubMed ID

  • 19168031
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Additional Document Info

start page

  • 87

end page

  • 92

volume

  • 380

issue

  • 1

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