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rdf:type |
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lifeskim:mentions |
umls-concept:C0007745,
umls-concept:C0033640,
umls-concept:C0038250,
umls-concept:C0439851,
umls-concept:C0439855,
umls-concept:C1167622,
umls-concept:C1335191,
umls-concept:C1515877,
umls-concept:C1522492,
umls-concept:C1552596,
umls-concept:C1709385,
umls-concept:C1879547,
umls-concept:C1947931
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pubmed:issue |
28
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pubmed:dateCreated |
2005-7-11
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pubmed:abstractText |
We have reported that ceramide mediates binding of atypical protein kinase C (PKC) zeta to its inhibitor protein, PAR-4 (prostate apoptosis response-4), thereby inducing apoptosis in differentiating embryonic stem cells. Using a novel method of lipid vesicle-mediated affinity chromatography, we showed here that endogenous ceramide binds directly to the PKCzeta.PAR-4 complex. Ceramide and its analogs activated PKCzeta prior to binding to PAR-4, as determined by increased levels of phosphorylated PKCzeta and glycogen synthase kinase-3beta and emergence of a PAR-4-to-phosphorylated PKCzeta fluorescence resonance energy transfer signal that co-localizes with ceramide. Elevated expression and activation of PKCzeta increased cell survival, whereas expression of PAR-4 promoted apoptosis. This suggests that PKCzeta counteracts apoptosis, unless its ceramide-induced activation is compromised by binding to PAR-4. A luciferase reporter assay showed that ceramide analogs activate nuclear factor (NF)-kappaB unless PAR-4-dependent inhibition of PKCzeta suppresses NF-kappaB activation. Taken together, our results show that direct physical association with ceramide and PAR-4 regulates the activity of PKCzeta. They also indicate that this interaction regulates the activity of glycogen synthase kinase-3beta and NF-kappaB.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ceramides,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylserines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta,
http://linkedlifedata.com/resource/pubmed/chemical/prostate apoptosis response-4...,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C zeta
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
26415-24
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:15901738-Actins,
pubmed-meshheading:15901738-Animals,
pubmed-meshheading:15901738-Apoptosis,
pubmed-meshheading:15901738-Apoptosis Regulatory Proteins,
pubmed-meshheading:15901738-Cell Differentiation,
pubmed-meshheading:15901738-Cell Survival,
pubmed-meshheading:15901738-Cells, Cultured,
pubmed-meshheading:15901738-Ceramides,
pubmed-meshheading:15901738-Chromatography,
pubmed-meshheading:15901738-DNA, Complementary,
pubmed-meshheading:15901738-Enzyme Activation,
pubmed-meshheading:15901738-Fluorescence Resonance Energy Transfer,
pubmed-meshheading:15901738-Genes, Reporter,
pubmed-meshheading:15901738-Glycogen Synthase Kinase 3,
pubmed-meshheading:15901738-Humans,
pubmed-meshheading:15901738-Immunohistochemistry,
pubmed-meshheading:15901738-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15901738-Lipid Metabolism,
pubmed-meshheading:15901738-Lipids,
pubmed-meshheading:15901738-Luciferases,
pubmed-meshheading:15901738-Mice,
pubmed-meshheading:15901738-Microscopy, Fluorescence,
pubmed-meshheading:15901738-Models, Biological,
pubmed-meshheading:15901738-NF-kappa B,
pubmed-meshheading:15901738-Phosphatidylserines,
pubmed-meshheading:15901738-Phosphorylation,
pubmed-meshheading:15901738-Plasmids,
pubmed-meshheading:15901738-Protein Binding,
pubmed-meshheading:15901738-Protein Kinase C,
pubmed-meshheading:15901738-Protein Structure, Tertiary,
pubmed-meshheading:15901738-Stem Cells,
pubmed-meshheading:15901738-Time Factors,
pubmed-meshheading:15901738-Transfection
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pubmed:year |
2005
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pubmed:articleTitle |
Direct binding to ceramide activates protein kinase Czeta before the formation of a pro-apoptotic complex with PAR-4 in differentiating stem cells.
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pubmed:affiliation |
Institute of Molecular Medicine and Genetics, School of Medicine, Medical College of Georgia, Augusta 30912, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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