AMP-activated protein kinase alpha 2 subunit (AMPKα2)

AMP-activated protein kinase alpha 2 subunit is one of the two catalytic subunits (alpha 1 and alpha 2) of the heterotrimeric AMPK complex, which serves as a master regulator of cellular energy homeostasis by sensing and responding to changes in the AMP/ATP ratio. The alpha 2 isoform (encoded by the PRKAA2 gene) is highly expressed in skeletal and cardiac muscle as well as liver, where it plays significant roles in increasing glucose uptake, enhancing fatty acid oxidation, inhibiting anabolic processes, and protecting against metabolic stress. Pharmacological activators of AMPKα2 include clinically used drugs like metformin and experimental agents, making it an important therapeutic target for type 2 diabetes, cardiovascular disease, obesity, certain cancers, and other metabolic disorders. Mechanistically, AMPKα2 exerts its effects through phosphorylation of multiple downstream targets, regulation of protein synthesis via mTOR inhibition, and modulation of transcription factors and metabolic enzymes. Dysregulation of AMPKα2 is implicated in insulin resistance, metabolic syndrome, and some skeletal diseases.

Other names

AMPK alpha-2 catalytic subunitPRKAA2 (gene symbol)AMPKα2AMPK alpha-2Protein kinase, AMP-activated, alpha 2 catalytic subunit

Allosteric activation by AMP and AMP mimetics; Direct phosphorylation of AMPKα2 by upstream kinases (e.g., LKB1, CaMKKβ); Inhibition of the mTOR pathway; Activation of catabolic and inhibition of anabolic processes.