Modulation of insulin-stimulated glycogen synthesis by Src Homology Phosphatase 2

Molecular and Cellular Endocrinology
D M OuwensJ A Maassen

Abstract

We have examined the requirement of the protein tyrosine phosphatase Src Homology Phosphatase 2 (SHP2) for insulin-stimulated glycogen synthesis. To this end, 3T3L1 fibroblasts were stably transfected with either wild type or a catalytically inactive C463A-mutant of SHP2, and analysed for insulin-induced glycogen synthesis, tyrosine phosphorylation of the insulin receptor and IRS-1, and activation of phosphatidylinositol 3'-kinase (PI 3'-kinase). Glycogen synthesis was stimulated 9.1+/-0.9-fold by insulin in untransfected cells. In cells expressing the dominant-negative C463A-SHP2 mutant, the stimulation of glycogen synthesis by insulin was strongly enhanced (18.7+/-2.7-fold stimulation), while this response was impaired in cells overexpressing wild-type SHP2 (6.6+/-1.1-fold stimulation). When exploring the early post-receptor signalling pathways that contribute to glycogen synthesis, we found that insulin stimulated the tyrosine phosphorylation of IRS-1, and the activation of IRS-1-associated PI 3'-kinase more strongly in C463A-SHP2 expressing 3T3L1-cells (18.1+/-4.7-fold) than in parental 3T3L1 cells (6.8+/-0.5-fold). In 3T3L1 cells overexpressing wild-type SHP2, the insulin stimulation of IRS-1 tyrosine phosphorylation and t...Continue Reading

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Citations

Jan 13, 2010·The Journal of Biological Chemistry·Ming-Fo Hsu, Tzu-Ching Meng
Sep 16, 2010·The Journal of Biological Chemistry·Kosuke MatsuoFawaz G Haj
Sep 6, 2015·European Journal of Medical Genetics·Mylène TajanArmelle Yart
Oct 23, 2016·Free Radical Biology & Medicine·Ming-Fo HsuTzu-Ching Meng
Aug 2, 2005·The Journal of Biological Chemistry·Karsten MüssigHans-Ulrich Häring
Mar 11, 2003·American Journal of Physiology. Endocrinology and Metabolism·Ernest Asante-Appiah, Brian P Kennedy
Nov 12, 2019·Frontiers in Immunology·Charlène NiogretGreta Guarda

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