5'-AMP-activated protein kinase subunit alpha-2, beta-2, gamma-1 heterotrimer (AMPK α2β2γ1)

5'-AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme complex that serves as a master regulator of cellular energy homeostasis (Hardie, 2012) [1]. The α2β2γ1 heterotrimer consists of the catalytic alpha-2 subunit (PRKAA2), the scaffolding beta-2 subunit (PRKAB2), and the regulatory gamma-1 subunit (PRKAG1) (UniProt P54646, O43741, P54619) [2, 3, 4]. This specific isoform combination is highly expressed in skeletal muscle and plays a critical role in stimulating glucose uptake and fatty acid oxidation during exercise or metabolic stress (Cokorinos et al., 2017) [5]. AMPK is activated by an increase in the AMP:ATP ratio, leading to the phosphorylation of downstream targets that shift the cell from an anabolic to a catabolic state (Hardie, 2012) [1]. Because of its ability to improve insulin sensitivity and reduce lipid accumulation, the AMPK α2β2γ1 complex is a major therapeutic target for metabolic disorders such as type 2 diabetes and obesity (Myers et al., 2017) [6]. Pharmacological activators of this complex, such as MK-8722, are being investigated for their potential to mimic the beneficial effects of exercise on metabolic health (Myers et al., 2017) [6]. Direct activators often target the Allosteric Drug and Metabolite (ADaM) site located between the alpha and beta subunits (Xiao et al., 2013) [7].

Other names

AMPK alpha-2 beta-2 gamma-1PRKAA2-PRKAB2-PRKAG1 complex5'-AMP-activated protein kinase alpha-2/beta-2/gamma-1AMP-activated protein kinase alpha-2/beta-2/gamma-1PRKAA2/PRKAB2/PRKAG1

AMPK is activated allosterically by AMP and ADP binding to the gamma subunit, which promotes phosphorylation of Thr172 in the alpha subunit by upstream kinases (LKB1, CaMKK2) and inhibits its dephosphorylation. Direct synthetic activators typically bind to the Allosteric Drug and Metabolite (ADaM) site located at the interface between the alpha-catalytic and beta-scaffolding subunits (Xiao et al., 2013) [7].