Regulation of glycogen synthetase. Specificity and stoichiometry of phosphorylation of the skeletal muscle enzyme by cyclic 3'5' AMP dependent protein kinase

T. R. Soderling

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    Abstract

    Complete conversion of skeletal muscle glycogen synthetase from the I form to the D form requires incorporation of 2 mol of phosphate per enzyme subunit (90,000 g). Incubation of synthetase I with low concentrations of adenosine 3':5' monophosphate (cAMP) dependent protein kinase (10 units/ml) and ATP (0.1 to 0.3 mM) plus magnesium acetate (10 mM) results in incorporation within half hr of 1 mol of phosphate per subunit concomitant with a decrease in the synthetase activity ratio (minus glucose 6 P/plus glucose 6P) from 0.85 to 0.25. Further incubation for 6 hr does not greatly increase the phosphate content of the synthetase or promote conversion to the D form. This level of phosphorylation is not increased by raising the concentration of protein kinase to 150 units/ml and is not influenced by the presence of glucose 6 P, UDP glucose, or glycogen. However, at protein kinase concentrations of 10,000 to 30,000 units/ml a second mol of phosphate is incorporated per subunit, and the synthetase activity ratio decreases to 0.05 or less. In addition to the 2 mol of phosphate per subunit which are required for formation of synthetase D, further phosphorylation can be observed which is not associated with changes in synthetase activity. This phosphorylation occurs at a slow rate, is increased by raising the ATP concentration to 2 to 4 mM, and is not blocked by the heat stable protein inhibitor of cAMP dependent protein kinase. These data indicate that skeletal muscle glycogen synthetase contains multiple phosphorylation sites only 2 of which are involved in the synthetase I to D conversion.

    Original languageEnglish (US)
    Pages (from-to)5407-5412
    Number of pages6
    JournalJournal of Biological Chemistry
    Volume250
    Issue number14
    StatePublished - Dec 1 1975

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    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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