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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1-2
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pubmed:dateCreated |
2007-3-26
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pubmed:abstractText |
A single nucleotide polymorphism in the partitioning defective protein-6alpha (Par6alpha) promoter is coupled with lower Par6alpha expression and better insulin sensitivity, whereas overexpression of Par6alpha in C2C12 myoblasts inhibits insulin-induced protein kinase B/Akt1 activation and glycogen synthesis. Here we show that a direct interaction of Par6alpha with atypical protein kinase C (aPKC) is crucial for this inhibition. A DeltaPB1-Par6alpha deletion mutant that does not interact with aPKC neither increased aPKC activity nor interfered with insulin-induced Akt1 activation in C2C12 cells. Further, T34 phosphorylation of Akt1 through aPKC is important for inhibition of Akt1. When Par6alpha was overexpressed, activation of wild-type Akt1 (-59.3%; p=0.049), but not T34A-Akt1 (+2.9%, p=0.41) was reduced after insulin stimulation. The resistance of T34A-Akt1 to Par6alpha/aPKC-mediated inhibition was also reflected by reconstitution of insulin-induced glycogen synthesis. In summary, Par6alpha-mediated inhibition of insulin-dependent glycogen synthesis in C2C12 cells depends on the direct interaction of Par6alpha with aPKC and on aPKC-mediated T34 phosphorylation of Akt1.
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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/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Mutant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PARD6A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PKC-3 protein,
http://linkedlifedata.com/resource/pubmed/chemical/Par6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphothreonine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0303-7207
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
268
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
30-6
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17335965-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:17335965-Animals,
pubmed-meshheading:17335965-Carrier Proteins,
pubmed-meshheading:17335965-Cell Line,
pubmed-meshheading:17335965-Down-Regulation,
pubmed-meshheading:17335965-Enzyme Activation,
pubmed-meshheading:17335965-Enzyme Inhibitors,
pubmed-meshheading:17335965-Glycogen,
pubmed-meshheading:17335965-Humans,
pubmed-meshheading:17335965-Insulin,
pubmed-meshheading:17335965-Mice,
pubmed-meshheading:17335965-Mice, Inbred C57BL,
pubmed-meshheading:17335965-Mutant Proteins,
pubmed-meshheading:17335965-Phosphorylation,
pubmed-meshheading:17335965-Phosphothreonine,
pubmed-meshheading:17335965-Protein Binding,
pubmed-meshheading:17335965-Protein Kinase C,
pubmed-meshheading:17335965-Protein Structure, Tertiary,
pubmed-meshheading:17335965-Proto-Oncogene Proteins c-akt
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pubmed:year |
2007
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pubmed:articleTitle |
The Par6alpha/aPKC complex regulates Akt1 activity by phosphorylating Thr34 in the PH-domain.
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pubmed:affiliation |
Department of Internal Medicine IV, University of Tübingen, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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