AMPK β Subunit Targets Metabolic Stress Sensing to Glycogen

摘要: Abstract AMP-activated protein kinase (AMPK) is a multisubstrate enzyme activated by increases in AMP during metabolic stress caused exercise, hypoxia, lack of cell nutrients [1], as well hormones, including adiponectin and leptin [2, 3]. Furthermore, metformin rosiglitazone, frontline drugs used for the treatment type II diabetes, activate AMPK [4]. Mammalian an αβγ heterotrimer with multiple isoforms each subunit comprising α1, α2, β1, β2, γ1, γ2, γ3, which have varying tissue subcellular expression [5, 6]. Mutations γ cause glycogen storage disease humans [7], but molecular relationship between AMPK/Snf1p subfamily has not been apparent. We show that β contains functional binding domain (β-GBD) most closely related to isoamylase domains found starch branching enzymes. Mutation key residues, predicted modeling, completely abolished β-GBD glycogen. binds retains full activity. Overexpressed β1 localized specific mammalian structures corresponded pattern phosphorylase. Glycogen provides architectural link major cellular energy store juxtaposes bound phosphatases.