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Stimulation of glycogen-targeted protein phosphatase 1 (PP1) activity by insulin contributes to the dephosphorylation and activation of hepatic gly-cogen synthase (GS) leading to an increase in glycogen synthesis. The gly-cogen-targeting subunits of PP1, GLand R5⁄PTG, are downregulated in the livers of diabetic rodents and restored by insulin treatment. We show here that the mammalian genePPP1R3Eencodes a novel glycogen-target-ing subunit of PP1 that is expressed in rodent liver. | iFEBS Journal A novel glycogen-targeting subunit of protein phosphatase 1 that is regulated by insulin and shows differential tissue distribution in humans and rodents Shonagh Munro1 Hugo Ceulemans2 Mathieu Bollen2 Julie Diplexcito1 and Patricia T.W. Cohen1 1 MedicalResearch CouncilProtein Phosphorylation Unit University of Dundee UK 2 Katholieke Universiteit Leuven Faculteit Geneeskunde Afdeling Biochemie Belgium Keywords diabetes glycogen metabolism glycogen synthase insulin PP1 Correspondence P. T. W. Cohen MRC Protein Phosphorylation Unit Schoolof Life Sciences MSI WTB Complex University of Dundee Dow Street Dundee DD1 5EH UK Fax 44 1382 223778 Tel 44 1382 344240 E-mail p.t.w.cohen@dundee.ac.uk Received 23 September 2004 revised 16 December 2004 accepted 26 January 2005 doi 10.1111 j.1742-4658.2005.04585.x Stimulation of glycogen-targeted protein phosphatase 1 PP1 activity by insulin contributes to the dephosphorylation and activation of hepatic glycogen synthase GS leading to an increase in glycogen synthesis. The glycogen-targeting subunits of PP1 GL and R5 PTG are downregulated in the livers of diabetic rodents and restored by insulin treatment. We show here that the mammalian gene PPP1R3E encodes a novel glycogen-targeting subunit of PP1 that is expressed in rodent liver. The phosphatase activity associated with R3E is slightly higher than that associated with R5 PTG and it is downregulated in streptozotocin-induced diabetes by 6070 and restored by insulin treatment. Surprisingly although mRNA for R3E is most highly expressed in rat liver and heart muscle with only low levels in skeletal muscle R3E mRNA is most abundant in human skeletal muscle and heart tissues with barely detectable levels in human liver. This species-specific difference in R3E mRNA expression has similarities to the high level of expression of GL mRNA in human but not rodent skeletal muscle. The observations imply that the mechanisms by which insulin regulates glycogen synthesis in liver
