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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 |
2001-3-6
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pubmed:abstractText |
Grb10 is a member of a family of adapter proteins that binds to tyrosine-phosphorylated receptors including the insulin receptor kinase (IRK). In this study recombinant adenovirus was used to over-express hGrb10zeta, a new Grb10 isoform, in primary rat hepatocytes and the consequences for insulin signaling were evaluated. Over-expression of hGrb10zeta resulted in 50% inhibition of insulin-stimulated IRK autophosphorylation and activation. Analysis of downstream events showed that hGrb10zeta over-expression specifically inhibits insulin-stimulated glycogen synthase (GS) activity and glycogen synthesis without affecting insulin-induced IRS1/2 phosphorylation, PI3-kinase activation, insulin like growth factor binding protein-1 (IGFBP-1) mRNA expression, and ERK1/2 MAP kinase activity. The classical pathway from PI3-kinase through Akt-PKB/GSK-3 leading to GS activation by insulin was also not affected by hGrb10zeta over-expression. These results indicate that hGrb10zeta inhibits a novel and presently unidentified insulin signaling pathway leading to GS activation in liver.
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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/Akt1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/GRB10 Adaptor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Organometallic Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Phenanthrolines,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/bisperoxo(1,10-phenanthroline)oxovan...,
http://linkedlifedata.com/resource/pubmed/chemical/insulin receptor serine kinase
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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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 |
28
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pubmed:volume |
173
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15-27
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:11223174-Animals,
pubmed-meshheading:11223174-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:11223174-Cells, Cultured,
pubmed-meshheading:11223174-Enzyme Activation,
pubmed-meshheading:11223174-GRB10 Adaptor Protein,
pubmed-meshheading:11223174-Glycogen,
pubmed-meshheading:11223174-Glycogen Synthase,
pubmed-meshheading:11223174-Glycogen Synthase Kinase 3,
pubmed-meshheading:11223174-Hepatocytes,
pubmed-meshheading:11223174-Humans,
pubmed-meshheading:11223174-Insulin,
pubmed-meshheading:11223174-Insulin-Like Growth Factor Binding Protein 1,
pubmed-meshheading:11223174-Male,
pubmed-meshheading:11223174-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11223174-Organometallic Compounds,
pubmed-meshheading:11223174-Phenanthrolines,
pubmed-meshheading:11223174-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11223174-Phosphorylation,
pubmed-meshheading:11223174-Protein Tyrosine Phosphatases,
pubmed-meshheading:11223174-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11223174-Proteins,
pubmed-meshheading:11223174-Proto-Oncogene Proteins,
pubmed-meshheading:11223174-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:11223174-RNA, Messenger,
pubmed-meshheading:11223174-Rats,
pubmed-meshheading:11223174-Rats, Sprague-Dawley,
pubmed-meshheading:11223174-Receptor, Insulin,
pubmed-meshheading:11223174-Signal Transduction,
pubmed-meshheading:11223174-Transcription, Genetic
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pubmed:year |
2001
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pubmed:articleTitle |
Specific inhibition by hGRB10zeta of insulin-induced glycogen synthase activation: evidence for a novel signaling pathway.
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pubmed:affiliation |
The Polypeptide Hormone Laboratory, McGill University, Strathcona Building, 3640 University Street, Quebec, H3A 2B2, Montreal, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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