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Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase.

Authors: Hawley, SA  Pan, DA  Mustard, KJ  Ross, L  Bain, J  Edelman, AM  Frenguelli, BG  Hardie, DG 
Citation: Hawley SA, etal., Cell Metab. 2005 Jul;2(1):9-19.
Pubmed: (View Article at PubMed) PMID:16054095
DOI: Full-text: DOI:10.1016/j.cmet.2005.05.009

The AMP-activated protein kinase (AMPK) is a critical regulator of energy balance at both the cellular and whole-body levels. Two upstream kinases have been reported to activate AMPK in cell-free assays, i.e., the tumor suppressor LKB1 and calmodulin-dependent protein kinase kinase. However, evidence that this is physiologically relevant currently only exists for LKB1. We now report that there is a significant basal activity and phosphorylation of AMPK in LKB1-deficient cells that can be stimulated by Ca2+ ionophores, and studies using the CaMKK inhibitor STO-609 and isoform-specific siRNAs show that CaMKKbeta is required for this effect. CaMKKbeta also activates AMPK much more rapidly than CaMKKalpha in cell-free assays. K(+)-induced depolarization in rat cerebrocortical slices, which increases intracellular Ca2+ without disturbing cellular adenine nucleotide levels, activates AMPK, and this is blocked by STO-609. Our results suggest a potential Ca(2+)-dependent neuroprotective pathway involving phosphorylation and activation of AMPK by CaMKKbeta.

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CRRD Object Information
CRRD ID: 2311420
Created: 2009-07-14
Species: All species
Last Modified: 2009-07-14
Status: ACTIVE



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