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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
1992-4-14
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pubmed:abstractText |
A sphingomyelin cycle has been identified whereby the action of certain extracellular agents results in reversible sphingomyelin hydrolysis and the concomitant generation of ceramide. Moreover, a cell-permeable ceramide, C2-ceramide (N-acetylsphingosine), is a potent modulator of cell proliferation and differentiation. We report herein that C2-ceramide, C6-ceramide, and natural ceramides activate a cytosolic serine/threonine protein phosphatase in a dose-dependent manner. Initial activation is observed at concentrations of ceramide as low as 0.1 microM with peak response occurring at 5-10 microM. However, other closely related sphingolipids, sphingosine and sphingomyelin, were largely inactive. Ceramide-stimulated phosphatase was inhibited by okadaic acid, an inhibitor of protein phosphatases, with an IC50 of 0.1-1 nM, depending on the concentration of ceramide. Ceramide-stimulated phosphatase was insensitive to Mg2+ and Mn2+ cations. Using sequential anion exchange chromatography, ceramide-stimulated phosphatase activity could be resolved from ceramide-nonresponsive phosphatases. The activity of partially purified enzyme was stimulated 3.5-fold by ceramide. The identification of a phosphatase as a molecular target for the action of ceramide defines a novel intracellular signaling pathway with potential roles in the regulation of cell proliferation and differentiation.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Ceramides,
http://linkedlifedata.com/resource/pubmed/chemical/Ethers, Cyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Okadaic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingomyelins,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
267
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5048-51
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:1312082-Cell Line,
pubmed-meshheading:1312082-Ceramides,
pubmed-meshheading:1312082-Chromatography, Ion Exchange,
pubmed-meshheading:1312082-Cytosol,
pubmed-meshheading:1312082-Ethers, Cyclic,
pubmed-meshheading:1312082-Humans,
pubmed-meshheading:1312082-Kinetics,
pubmed-meshheading:1312082-Okadaic Acid,
pubmed-meshheading:1312082-Phosphoprotein Phosphatases,
pubmed-meshheading:1312082-Phosphorylation,
pubmed-meshheading:1312082-Sphingomyelins,
pubmed-meshheading:1312082-Sphingosine
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pubmed:year |
1992
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pubmed:articleTitle |
Ceramide stimulates a cytosolic protein phosphatase.
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pubmed:affiliation |
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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