| DOI | Resolve DOI: https://doi.org/10.1016/S0303-7207(00)00439-1 |
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| Author | Search for: Mounier, Catherine; Search for: Lavoie, Louis; Search for: Dumas, Victor; Search for: Mohammad-Ali, Khosro; Search for: Wu, Jiong; Search for: Nantel, André1; Search for: Bergeron, John J. M.; Search for: Thomas, David Y.1; Search for: Posner, Barry I. |
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| Name affiliation | - National Research Council of Canada. NRC Biotechnology Research Institute
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| Format | Text, Article |
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| ISSN | 0303-7207 |
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| Subject | pharmaceutical; insulin; hGrb10ζ; hepatocytes; PI3-kinase; glycogen synthase; GSK-3; Akt/PKB; 1-phosphatidylinositol 3-kinase; calcium-calmodulin-dependent protein kinases; cells, cultured; enzyme activation; glycogen; glycogen synthase kinase 3; GRB10 adaptor protein; Insulin-like growth factor binding protein 1; male; mitogen-activated protein kinases; organometallic compounds; phenanthrolines; phosphorylation; protein tyrosine phosphatases; protein-serine-threonine kinases; protein; proto-Oncogene Proteins; proto-Oncogene Proteins c-akt; rat; rats, sprague-dawley; receptor, insulin; RNA, messenger; signal transduction; transcription, genetic |
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| Abstract | 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 hGrb10ζ, a new Grb10 isoform, in primary rat hepatocytes and the consequences for insulin signaling were evaluated. Over-expression of hGrb10ζ resulted in 50% inhibition of insulin-stimulated IRK autophosphorylation and activation. Analysis of downstream events showed that hGrb10z 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 hGrb10ζ over-expression. These results indicate that hGrb10ζ inhibits a novel and presently unidentified insulin signaling pathway leading to GS activation in liver. |
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| Publication date | 2001-02-19 |
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| In | |
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| Language | English |
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| Identifier | 10143968 |
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| NRC number | 44778 |
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| NPARC number | 3539576 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 612aba11-a4df-4de6-96b8-5015199b0cd5 |
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| Record created | 2009-03-01 |
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| Record modified | 2020-03-27 |
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