title: Control of glycogen synthesis in cultured human muscle cells.
abstract: The regulation of glycogen synthesis and associated enzymes was studied in human myoblasts and myotubes maintained in culture. Both epidermal growth factor (EGF) and insulin stimulated glycogen synthesis approximately 2-fold, this stimulation being accompanied by a rapid and stable activation of the controlling enzyme glycogen synthase (GS). EGF also caused inhibition of glycogen synthase kinase 3 (GSK-3) and activation of the alpha isoform of protein kinase B (PKB) with the time-course and magnitude of its effects being similar to those induced by insulin. An inhibitor of the mitogen-activated protein (MAP) kinase pathway did not prevent stimulation of GS by EGF, suggesting that this pathway is not essential for the effect. A partial decrease in the fold activation of GS was, however, observed when p70(S6k) activation was blocked with rapamycin, suggesting a contribution of this pathway to the control of GS by either hormone. Wortmannin, a selective inhibitor of phosphatidylinositol 3'-kinase (PI-3 kinase) completely blocked the effects of both EGF and insulin in these cells. These results demonstrate that EGF, like insulin, activates glycogen synthesis in muscle, acting principally via the PKB/GSK-3 pathway but with a contribution from a rapamycin-sensitive component that lies downstream of PI-3 kinase.
authors.affiliation: School of Biochemistry and Genetics, The Medical School, University of Newcastle upon Tyne, NE2 4HH, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Halse
authors.forename: J J
authors.initials: JJ
authors.lastname: Rochford
authors.forename: J G
authors.initials: JG
authors.lastname: McCormack
authors.forename: J R
authors.initials: JR
authors.lastname: Vandenheede
authors.forename: B A
authors.initials: BA
authors.lastname: Hemmings
authors.forename: S J
authors.initials: SJ
authors.lastname: Yeaman
mesh_terms: D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000502:physiology; D006003:Glycogen / Q000096:biosynthesis*; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt
chemical_list: D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D004815:Epidermal Growth Factor; D006003:Glycogen; D038341:Glycogen Synthase Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3