Source:http://linkedlifedata.com/resource/pubmed/id/16216880
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
49
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| pubmed:dateCreated |
2005-12-5
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| pubmed:abstractText |
Protein kinase C (PKC)-alpha exerts a regulatory function on insulin action. We showed by overlay blot that PKCalpha directly binds a 180-kDa protein, corresponding to IRS-1, and a 30-kDa molecular species, identified as 14-3-3epsilon. In intact NIH-3T3 cells overexpressing insulin receptors (3T3-hIR), insulin selectively increased PKCalpha co-precipitation with IRS-1, but not with IRS-2, and with 14-3-3epsilon, but not with other 14-3-3 isoforms. Overexpression of 14-3-3epsilon in 3T3-hIR cells significantly reduced IRS-1-bound PKCalpha activity, without altering IRS-1/PKCalpha co-precipitation. 14-3-3epsilon overexpression also increased insulin-stimulated insulin receptor and IRS-1 tyrosine phosphorylation, followed by increased activation of Raf1, ERK1/2, and Akt/protein kinase B. Insulin-induced glycogen synthase activity and thymidine incorporation were also augmented. Consistently, selective depletion of 14-3-3epsilon by antisense oligonucleotides caused a 3-fold increase of IRS-1-bound PKCalpha activity and a similarly sized reduction of insulin receptor and IRS-1 tyrosine phosphorylation and signaling. In turn, selective inhibition of PKCalpha expression by antisense oligonucleotides reverted the negative effect of 14-3-3epsilon depletion on insulin signaling. Moreover, PKCalpha inhibition was accompanied by a >2-fold decrease of insulin degradation. Similar results were also obtained by overexpressing 14-3-3epsilon. Thus, in NIH-3T3 cells, insulin induces the formation of multimolecular complexes, including IRS-1, PKCalpha, and 14-3-3epsilon. The presence of 14-3-3epsilon in the complex is not necessary for IRS-1/PKCalpha interaction but modulates PKCalpha activity, thereby regulating insulin signaling and degradation.
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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/14-3-3 Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/IRS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Irs1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
9
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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 |
40642-9
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:16216880-14-3-3 Proteins,
pubmed-meshheading:16216880-Animals,
pubmed-meshheading:16216880-Blotting, Western,
pubmed-meshheading:16216880-Gene Expression,
pubmed-meshheading:16216880-Gene Silencing,
pubmed-meshheading:16216880-Glycogen Synthase,
pubmed-meshheading:16216880-Humans,
pubmed-meshheading:16216880-Immunosorbent Techniques,
pubmed-meshheading:16216880-Insulin,
pubmed-meshheading:16216880-Insulin Receptor Substrate Proteins,
pubmed-meshheading:16216880-Mice,
pubmed-meshheading:16216880-NIH 3T3 Cells,
pubmed-meshheading:16216880-Oligonucleotides, Antisense,
pubmed-meshheading:16216880-Phosphoproteins,
pubmed-meshheading:16216880-Protein Kinase C-alpha,
pubmed-meshheading:16216880-Receptor, Insulin,
pubmed-meshheading:16216880-Recombinant Proteins,
pubmed-meshheading:16216880-Signal Transduction,
pubmed-meshheading:16216880-Thymidine,
pubmed-meshheading:16216880-Transfection
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| pubmed:year |
2005
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| pubmed:articleTitle |
Protein kinase C-alpha regulates insulin action and degradation by interacting with insulin receptor substrate-1 and 14-3-3 epsilon.
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| pubmed:affiliation |
Dipartimento di Biologia e Patologia Cellulare e Molecolare and Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Federico II University of Naples, Italy.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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