Specific inhibition by hGRB10zeta of insulin-induced glycogen synthase activation: evidence for a novel signaling pathway

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DOIResolve DOI: http://doi.org/10.1016/S0303-7207(00)00439-1
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TypeArticle
Journal titleMolecular and Cellular Endocrinology
ISSN0303-7207
Volume173
Issue1-2
Pages1527; # of pages: 13
Subjectpha; insulin; hGrb10ζ; hepatocytes; PI3-kinase; glycogen synthase; GSK-3; Akt/PKB; 1-phosphatidylinositol 3-kinase; animals; calcium-calmodulin-dependent protein kinases; cells, cultured; enzyme activation; glycogen; glycogen synthase kinase 3; GRB10 adaptor protein; humans; Insulin-like growth factor binding protein 1; male; mitogen-activated protein kinases; organometallic compounds; phenanthrolines; phosphorylation; protein tyrosine phosphatases; protein-serine-threonine kinases; proteins; proto-Oncogene Proteins; proto-Oncogene Proteins c-akt; rats; rats, sprague-dawley; receptor, insulin; RNA, messenger; signal transduction; transcription, genetic
AbstractGrb10 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.
Publication date
LanguageEnglish
AffiliationNRC Biotechnology Research Institute; National Research Council Canada
Peer reviewedNo
Identifier10143968
NRC number44778
NPARC number3539576
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Record identifier612aba11-a4df-4de6-96b8-5015199b0cd5
Record created2009-03-01
Record modified2016-05-09
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