AMP-activated protein kinase: greater AMP dependence, and preferential nuclear localization, of complexes containing the α2 isoform

DOI PDF 被引用文献6件
  • Ian SALT
    Biochemistry Department, The University, Dundee DD1 4HN, Scotland, U.K.
  • Jakub W. CELLER
    Biochemistry Department, The University, Dundee DD1 4HN, Scotland, U.K.
  • Simon A. HAWLEY
    Biochemistry Department, The University, Dundee DD1 4HN, Scotland, U.K.
  • Alan PRESCOTT
    Biochemistry Department, The University, Dundee DD1 4HN, Scotland, U.K.
  • Angela WOODS
    MRC Molecular Medicine Group, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, U.K.
  • David CARLING
    MRC Molecular Medicine Group, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, U.K.
  • D. Grahame HARDIE
    Biochemistry Department, The University, Dundee DD1 4HN, Scotland, U.K.

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<jats:p>Mammalian AMP-activated protein kinase (AMPK) is the downstream component of a cascade that is activated by cellular stresses associated with ATP depletion. AMPK exists as heterotrimeric αβγ complexes, where the catalytic subunit has two isoforms (α1 and α2) with different tissue distributions. The budding yeast homologue is the SNF1 kinase complex, which is essential for derepression of glucose-repressed genes, and seems to act by the direct phosphorylation of transcription factors in the nucleus. AMPK complexes containing the α2 rather than the α1 isoform have a greater dependence on AMP (approx. 5-fold stimulation compared with approx. 2-fold) both in direct allosteric activation and in reactivation by the upstream kinase. We have also examined their subcellular localization by using Western blotting of nuclear preparations, and by using two detection methods in the confocal microscope, i.e. indirect immunofluorescence of endogenous proteins and transfection of DNA species encoding green fluorescent protein–α-subunit fusions. By all three methods a significant proportion of α2, but not α1, is localized in the nucleus. Like SNF1, AMPK-α2 complexes could therefore be involved in the direct regulation of gene expression. The observed differences in the regulation of α1 and α2 complexes by AMP might result in differential responses to ATP depletion in distinct cellular and subcellular locations.</jats:p>

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