AMP-activated protein kinase gamma subunit (AMPK gamma)

The AMP-activated protein kinase (AMPK) gamma subunit is a regulatory component of the heterotrimeric AMPK complex, acting as the primary sensor for cellular energy status (Hardie, 2014). It contains four Cystathionine beta-synthase (CBS) domains that form binding sites for adenine nucleotides, allowing the complex to respond to changes in the AMP:ATP and ADP:ATP ratios (Xiao et al., 2013). When energy levels are low, the binding of AMP or ADP to the gamma subunit triggers a conformational change that allosterically activates the catalytic alpha subunit and protects it from dephosphorylation at Thr172 (UniProt Consortium, 2023). This activation promotes catabolic processes like glucose uptake and fatty acid oxidation while inhibiting anabolic pathways to restore energy balance. In humans, three isoforms (gamma-1, gamma-2, and gamma-3) exist with tissue-specific expressions; for instance, mutations in the PRKAG2 isoform are associated with cardiac hypertrophy and Wolff-Parkinson-White syndrome (Gollob et al., 2001). Consequently, the AMPK gamma subunit is a significant therapeutic target for metabolic diseases, including type 2 diabetes and obesity, as well as certain cancers (Hardie, 2014).

Other names

PRKAG5'-AMP-activated protein kinase subunit gammaProtein kinase AMP-activated non-catalytic subunit gammaAMPK gamma-1 (PRKAG1)AMPK gamma-2 (PRKAG2)AMPK gamma-3 (PRKAG3)

Allosteric activation of the AMPK complex through the binding of AMP or ADP to the CBS domains of the gamma subunit, which facilitates phosphorylation and prevents dephosphorylation of the catalytic alpha subunit (Hardie, 2014; Xiao et al., 2013).