The AMP-activated/SNF1 protein kinase subfamily: Metabolic sensors of the eukaryotic cell?

D. Grahame Hardie, David Carling, Marian Carlson

    Research output: Contribution to journalReview articlepeer-review

    1295 Citations (Scopus)

    Abstract

    Mammalian AMP-activated protein kinase and yeast SNF1 protein kinase are the central components of kinase cascades that are highly conserved between animals, fungi, and plants. The AMP-activated protein kinase cascade acts as a metabolic sensor or "fuel gauge" that monitors cellular AMP and ATP levels because it is activated by increases in the AMP:ATP ratio. Once activated, the enzyme switches off ATP-consuming anabolic pathways and switches on ATP-producing catabolic pathways, such as fatty acid oxidation. The SNF1 complex in yeast is activated in response to the stress of glucose deprivation. In this case the intracellular signal or signals have not been identified; however, SNF1 activation is associated with depletion of ATP and elevation of AMP. The SNF1 complex acts primarily by inducing expression of genes required for catabolic pathways that generate glucose, probably by triggering phosphorylation of transcription factors. SNF1-related protein kinases in higher plants are likely to be involved in the response of plant cells to environmental and/or nutritional stress.

    Original languageEnglish
    Pages (from-to)821-855
    Number of pages35
    JournalAnnual Review of Biochemistry
    Volume67
    DOIs
    Publication statusPublished - Jul 1998

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