AMP-activated protein kinase

D. Grahame Hardie (Lead / Corresponding author)

    Research output: Chapter in Book/Report/Conference proceedingChapter

    2 Citations (Scopus)

    Abstract

    The AMP-activated protein kinase (AMPK) is the downstream component of a kinase cascade that has multiple cellular targets. AMPK can be regulated by hormones and cytokines, especially those involved in regulating whole body energy balance, such as leptin, adiponectin, and ghrelin. Genome sequencing suggests that protein kinases related to AMPK exist in almost all eukaryotes, including protozoa, fungi, and plants, as well as invertebrates and vertebrates. AMP-activated/SNF1 protein kinases are heterotrimeric complexes consisting of a catalytic ß subunit and regulatory ß and ß subunits. AMPK/SNF1 complexes are essentially inactive unless phosphorylated on a threonine residue within the "activation loop" of the ß subunit by upstream kinases. AMPK complexes are allosterically activated by AMP, depending on the isoform composition and the exact conditions. A quantitatively more important effect is that AMP also promotes phosphorylation at Thr-172. The AMPK system is activated in intact cells by stresses that inhibit ATP production or accelerate ATP consumption. Stresses of the former type include heat stress and metabolic poisons, ischemia and hypoxia, osmotic and oxidative stress, and glucose deprivation. A physiological stress that activates AMPK by increasing ATP consumption is exercise in muscle. AMPK is responsible for the ability of adiponectin to stimulate fatty acid oxidation in muscle and inhibit glucose production in liver, and to increase food intake by effects on the hypothalamus. That is why the AMPK system is receiving increasing attention from medical scientists researching various different conditions, from obesity, diabetes, and cancer to heart disease.
    Original languageEnglish
    Title of host publicationHandbook of cell signaling
    EditorsRalph A. Bradshaw, Edward A. Dennis
    Place of PublicationLondon
    PublisherAcademic Press
    Pages551-557
    Number of pages7
    Volume2
    Edition2nd
    ISBN (Print)9780123741455, 9780123741479
    DOIs
    Publication statusPublished - 2010

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  • Cite this

    Hardie, D. G. (2010). AMP-activated protein kinase. In R. A. Bradshaw, & E. A. Dennis (Eds.), Handbook of cell signaling (2nd ed., Vol. 2, pp. 551-557). Academic Press. https://doi.org/10.1016/B978-0-12-374145-5.00073-5