Distinctive regulatory and metabolic properties of glycogen-targeting subunits of protein phosphatase-1 (PTG, G(L), G(M)/R(G1)) expressed in hepatocytes

Rosa Gasa, Per B. Jensen, Hal K. Berman, Matthew J. Brady, Anna A. Depaoli-Roach, Christopher B. Newgard

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Glycogen-targeting subunits of protein phosphatase-1 facilitate interaction of the phosphatase with enzymes of glycogen metabolism. We have shown that overexpression of one member of the family, protein targeting to glycogen (PTG), causes large increases in glycogen storage in isolated hepatocytes or intact rat liver. In the current study, we have compared the metabolic and regulatory properties of PTG (expressed in many tissues), with two other members of the gene family, G(L) (expressed primarily in liver) and G(M)/R(G1) (expressed primarily in striated muscle). Adenovirus-mediated expression of these proteins in hepatocytes led to the following key observations. 1) G(L) has the highest glycogenic potency among the three forms studied. 2) Glycogen synthase activity ratio is much higher in G(L)-overexpressing cells than in PTG or G(M)/R(G1)-overexpressing cells. Thus, at moderate levels of G(L) overexpression, glycogen synthase activity is increased by insulin treatment, but at higher levels of G(L) expression, insulin is no longer required to achieve maximal synthase activity. In contrast, cells with high levels of PTG overexpression retain dose-dependent regulation of glycogen synthesis and glycogen synthase enzyme activity by insulin. 3) G(L)- and G(M)/R(G1)-overexpressing cells exhibit a strong glycogenolytic response to forskolin, whereas PTG-overexpressing cells are less responsive. This difference may be explained in part by a lesser forskolin-induced increase in glycogen phosphorylase activity in PTG-overexpressing cells. Based on these results, we suggest that expression of either G(L) or G(M)/R(G1) in liver of diabetic animals may represent a strategy for lowering of blood glucose levels in diabetes.

Original languageEnglish (US)
Pages (from-to)26396-26403
Number of pages8
JournalJournal of Biological Chemistry
Issue number34
StatePublished - Aug 25 2000


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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