title: AMPKβ subunits: more than just a scaffold in the formation of AMPK complex.
abstract: AMP-activated protein kinase (AMPK) is a sensor of energy status composed of a catalytic subunit (AMPKα), a scaffolding subunit (AMPKβ) and a regulatory subunit involved in nucleotide binding (AMPKγ). Activation of AMPK results in enhancement of catabolic processes and downregulation of anabolic pathways with the aim to equilibrate the energy status of the cell. The study of the regulation of the activity of the AMPK complex has been traditionally focused on modifications of AMPKα and AMPKγ subunits by post-translational changes (i.e. phosphorylation of the catalytic subunit) and allosteric activation by AMP. In this review, we summarize recent reports that indicate that AMPKβ subunits are also critical players in AMPK function, because they can regulate the phosphorylation status and activity of the AMPK complex. AMPKβ1- and AMPKβ2-containing complexes differ in their capacity to be activated by specific drugs (i.e. A769622, salicylate) and also by the ability to undergo post-translational modifications. This selective behavior opens the possibility to design specific drugs that activate AMPK complexes containing specific β-isoforms.
authors.affiliation: Instituto de Biomedicina de Valencia, CSIC and Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain. sanz@ibv.csic.es
authors.forename: Pascual
authors.initials: P
authors.lastname: Sanz
authors.forename: Teresa
authors.initials: T
authors.lastname: Rubio
authors.forename: Maria Adelaida
authors.initials: MA
authors.lastname: Garcia-Gimeno
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D021122:Protein Subunits; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; activators; carbohydrate-binding module; heterotrimeric complex; myristoylation; phosphorylation; posttranslational modification; structural analysis; sumoylation; ubiquitination