The Recruitment of AMP-activated Protein Kinase to Glycogen Is Regulated by Autophosphorylation

Yvonne Oligschlaeger, Marie Miglianico, Dipanjan Chanda, Roland Scholz, Ramon F. Thali, Roland Tuerk, David I. Stapleton, Paul R. Gooley, Dietbert Neumann*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    The mammalian AMP-activated protein kinase (AMPK) is an obligatory alpha beta gamma heterotrimeric complex carrying a carbohydrate-binding module (CBM) in the beta-subunit (AMPK beta) capable of attaching AMPK to glycogen. Nonetheless, AMPK localizes at many different cellular compartments, implying the existence of mechanisms that prevent AMPK from glycogen binding. Cell-free carbohydrate binding assays revealed that AMPK autophosphorylation abolished its carbohydrate-binding capacity. X-ray structural data of the CBM displays the central positioning of threonine 148 within the binding pocket. Substitution of Thr-148 for a phospho-mimicking aspartate (T148D) prevents AMPK from binding to carbohydrate. Overexpression of isolated CBM or beta 1-containing AMPK in cellular models revealed that wild type( WT) localizes to glycogen particles, whereas T148D shows a diffuse pattern. Pharmacological AMPK activation and glycogen degradation by glucose deprivation but not forskolin enhanced cellular Thr-148 phosphorylation. Cellular glycogen content was higher if pharmacological AMPK activation was combined with overexpression of T148D mutant relative to WT AMPK. In summary, these data show that glycogen-binding capacity of AMPK beta is regulated by Thr-148 autophosphorylation with likely implications in the regulation of glycogen turnover. The findings further raise the possibility of regulated carbohydrate-binding function in a wider variety of CBM-containing proteins.
    Original languageEnglish
    Pages (from-to)11715-11728
    JournalJournal of Biological Chemistry
    Volume290
    Issue number18
    DOIs
    Publication statusPublished - 1 May 2015

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