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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1998-2-23
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pubmed:abstractText |
We previously reported that insulin activates nuclear factor kappaB (NF-kappaB) in Chinese hamster ovary (CHO)-R cells overexpressing wild-type insulin receptors (IRs) through a pathway requiring IR tyrosine kinase and Raf-1 kinase activities. We now investigated whether the activation of NF-kappaB by insulin could serve an antiapoptotic function. Insulin (10(-9)-10(-7) M) inhibited apoptosis induced by serum withdrawal in CHO-R cells in a concentration-dependent manner. Insulin antiapoptotic signaling: (i) was dependent on IR number and IR tyrosine kinase activity since it was reduced in parental CHO cells and was abolished in CHO-Y2 cells overexpressing IRs mutated at Tyr1162/1163; (ii) was, like insulin activation of NF-kappaB, dependent on Raf-1 but not on mitogen-activated protein kinase activity since both processes were decreased by the dominant-negative Raf-1 mutant Raf-C4 whereas they persisted in mitogen-activated protein kinase-depleted cells; and (iii) required NF-kappaB activation since it was decreased by proteasome inhibitors and the dominant-negative IkappaB-alpha (A32/36) mutant and was mimicked by overexpression of the NF-kappaB c-Rel subunit. We also show that insulin antiapoptotic signaling but not insulin activation of NF-kappaB involved phosphatidylinositol 3-kinase (PI 3-kinase), as supported by the inhibition of the former but not of the latter process by the PI 3-kinase inhibitor LY294002. Inhibition of both NF-kappaB and PI 3-kinase totally abolished insulin antiapoptotic signaling. Thus insulin exerts a specific antiapoptotic function which is dependent on IR tyrosine kinase activity and is mediated by both a Raf-1-dependent pathway that leads to NF-kappaB activation and a PI 3-kinase-dependent pathway.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-raf,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonyl-isoleucyl-glutamyl...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2931-8
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:9446605-Animals,
pubmed-meshheading:9446605-Apoptosis,
pubmed-meshheading:9446605-CHO Cells,
pubmed-meshheading:9446605-Chromones,
pubmed-meshheading:9446605-Cricetinae,
pubmed-meshheading:9446605-Insulin,
pubmed-meshheading:9446605-Morpholines,
pubmed-meshheading:9446605-NF-kappa B,
pubmed-meshheading:9446605-Oligopeptides,
pubmed-meshheading:9446605-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:9446605-Proto-Oncogene Proteins c-raf,
pubmed-meshheading:9446605-Receptor, Insulin,
pubmed-meshheading:9446605-Signal Transduction
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pubmed:year |
1998
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pubmed:articleTitle |
A role for nuclear factor kappaB in the antiapoptotic function of insulin.
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pubmed:affiliation |
INSERM U.402, Institut Fédératif de Recherche 65, Laboratoire de Biologie Cellulaire, Faculté de Médecine Saint-Antoine, 27 rue Chaligny, 75571 Paris, Cedex 12, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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