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Sphingosine kinase‐1 compartmentalization drives downstream metabolism of sphingosine‐1‐phosphate and upstream metabolism of ceramide biosynthesis
Author(s) -
Wattenberg Binks,
Siow Deanna,
Berdyshev Evgeny,
Pitson Stuart,
Anderson Charles
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.312.2
Subject(s) - endoplasmic reticulum , sphingosine kinase , ceramide , sphingolipid , sphingosine , microbiology and biotechnology , lipid signaling , compartmentalization (fire protection) , biochemistry , biology , sphingosine 1 phosphate , lipid metabolism , signal transduction , kinase , chemistry , enzyme , apoptosis , receptor
Sphingosine kinase (SK) is a ubiquitous lipid signaling enzyme that produces the potent signaling lipid sphingosine‐1‐phosphate (S1P). SK has a dual function as a signaling enzyme and as a key regulator of sphingolipid metabolism. In this work we focus on the consequences of subcellular compartmentalization of SK on the metabolism of S1P. We find that the targeting of SK‐1 to either the endoplasmic reticulum or the plasma membrane promotes degradation of S1P by both a S1P lyase and phosphatases. Both sets of enzymes appear to contribute to this degradation equally. Surprisingly we find that association of SK to the endoplasmic reticulum promotes a dramatic increase in dihydro‐S1P. Dihydrosphingosine is the metabolic precursor for ceramide formation by the de novo pathway. Our data suggests that association of SK dwith the endoplasmic reticulum drains dihydrosphingosine from the ceramide synthetic pathway. Plasma membrane‐associated SK does not have this effect. Our data suggests that both the fate of S1P as a second messenger, and the metabolism of sphingosine metabolites is controlled by the subcellular localization of SK.