The 5 AMP activated protein kinase (AMPK), a member of the SNF1 (sucrose non fermentor) kinase family, is a heterotrimeric protein comprise of alpha (63 kDa), beta (30 kDa) and gamma (38 kDa) subunits. The alpha subunit is the catalytic subunit, while beta and gamma are non catalytic subunits (although they have been found to interact with the active subunit in liver). AMPK regulates fatty acid and sterol synthesis by phosphorylation of acetyl CoA as well as cholesterol synthesis via phosphorylation and inactivation of hydroxymethylglutaryl CoA reductase. AMPK is activated by AMP and can be also regulated by treatment with purified protein phosphatase in vitro.
Function: AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.
Subunit: AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2.
Subcellular Location: Cytosol; Nucleus
Post-translational modifications: Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK.
Similarity: Belongs to the 5'-AMP-activated protein kinase gamma subunit family.
