The Glycogen-Binding Domain on the AMPK β Subunit Allows the Kinase to Act as a Glycogen Sensor

Andrew McBride, Stephanos Ghilagaber, Andrei Nikolaev, D. Grahame Hardie (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    267 Citations (Scopus)

    Abstract

    AMPK beta subunits contain a conserved domain that causes association with glycogen. Although glycogen availability is known to affect AMPK regulation in vivo, the molecular mechanism for this has not been clear. We now show that AMPK is inhibited by glycogen, particularly preparations with high branching content. We synthesized a series of branched oligosaccharides and show that those with a single alpha 1 -> 6 branch are allosteric inhibitors that also inhibit phosphorylation by upstream kinases. Removal of the outer chains of glycogen using phosphorylase, thus exposing the outer branches, renders inhibition of AMPK more potent. Inhibition by all carbohydrates tested was dependent on the glycogen-binding domain being abolished by mutation of residues required for carbohydrate binding. Our results suggest the hypothesis that AMPK, as well as monitoring immediate energy availability by sensing AMP/ATP, may also be able to sense the status of cellular energy reserves in the form of glycogen.

    Original languageEnglish
    Pages (from-to)23-34
    Number of pages12
    JournalCell Metabolism
    Volume9
    Issue number1
    DOIs
    Publication statusPublished - 7 Jan 2009

    Keywords

    • ACTIVATED PROTEIN-KINASE
    • HUMAN SKELETAL-MUSCLE
    • RAT-LIVER
    • STRUCTURAL BASIS
    • UPSTREAM KINASE
    • SYNTHASE
    • GLUCOSE
    • EXERCISE
    • PHOSPHORYLATION
    • METABOLISM

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