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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1995-3-16
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pubmed:abstractText |
This study was undertaken to define intracellular signaling pathways upstream to glycogen synthase activation. First, we examined the role of the two pathways of insulin signaling, Ras-dependent and wortmannin/LY294002-sensitive, in glycogen synthase activation. Although negative dominant Ras (Ras17N) induction in PC12 cells markedly decreased activities of mitogen-activated protein kinase (MAP) and pp90 S6 kinase in response to insulin or insulin-like growth factor I (IGF-I), activation of glycogen synthase by these agents was unaffected by negative dominant Ras induction. In contrast, wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), inhibitors of phosphatidylinositol 3-kinase, antagonized glycogen synthase activation in response to insulin or IGF-I. Next, we examined the contribution of pp70 S6 kinase, one of the wortmannin/LY294002-sensitive signaling molecules on glycogen synthase activation. Immunosuppressant rapamycin completely blocked activation of pp70 S6 kinase by insulin or IGF-I, but rapamycin alone or in combination with induction of negative dominant Ras failed to antagonize glycogen synthase activation by these hormones. These data suggest that 1) activation of Ras-MAP kinase is not necessary for stimulation of glycogen synthase and 2) activation of wortmannin/LY294002-sensitive pathway, independent of pp70 S6 kinase, plays a key role in glycogen synthase regulation in PC12 cells.
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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/Androstadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein p21(ras),
http://linkedlifedata.com/resource/pubmed/chemical/Polyenes,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus,
http://linkedlifedata.com/resource/pubmed/chemical/wortmannin
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
270
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
2729-34
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:7852343-Amino Acid Sequence,
pubmed-meshheading:7852343-Androstadienes,
pubmed-meshheading:7852343-Animals,
pubmed-meshheading:7852343-Chromones,
pubmed-meshheading:7852343-Enzyme Activation,
pubmed-meshheading:7852343-Glycogen Synthase,
pubmed-meshheading:7852343-Insulin,
pubmed-meshheading:7852343-Insulin-Like Growth Factor I,
pubmed-meshheading:7852343-Molecular Sequence Data,
pubmed-meshheading:7852343-Morpholines,
pubmed-meshheading:7852343-Oncogene Protein p21(ras),
pubmed-meshheading:7852343-PC12 Cells,
pubmed-meshheading:7852343-Polyenes,
pubmed-meshheading:7852343-Protein-Serine-Threonine Kinases,
pubmed-meshheading:7852343-Rats,
pubmed-meshheading:7852343-Ribosomal Protein S6 Kinases,
pubmed-meshheading:7852343-Sirolimus
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pubmed:year |
1995
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pubmed:articleTitle |
Upstream mechanisms of glycogen synthase activation by insulin and insulin-like growth factor-I. Glycogen synthase activation is antagonized by wortmannin or LY294002 but not by rapamycin or by inhibiting p21ras.
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pubmed:affiliation |
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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