5'-AMP-activated protein kinase catalytic subunit alpha (PRKAA or AMPKalpha) is the catalytic subunit of the AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism []. There are two AMPK alpha-subunit isoforms in mammals: PRKAA1 and PRKAA2. They have an N-terminal Ser/Thr kinase domain followed by an ubiquitin-associated (UBA)-like AID and a C-terminal AMPK regulatory domain [].This entry represents the AID that is responsible for PRKAA autoinhibition.
5'-AMP-activated protein kinase catalytic subunit alpha (PRKAA) is the catalytic subunit of the AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism []. There are two AMPK alpha-subunit isoforms in mammals: PRKAA1 and PRKAA2. They have an N-terminal Ser/Thr kinase domain followed by an ubiquitin-associated (UBA)-like AID and a C-terminal AMPK regulatory domain [].This entry represents the AID that is responsible for PRKAA autoinhibition. PRKAA2 has been associated with type 2 diabetes [, ].
AMPK, a serine/threonine protein kinase (STK), catalyzes the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. It acts as a sensor for the energy status of the cell and is activated by cellular stresses that lead to ATP depletion such as hypoxia, heat shock, and glucose deprivation, among others. AMPK is a heterotrimer of three subunits: alpha, beta, and gamma []. The alpha subunit is the catalytic subunit and it contains an N-terminal kinase domain, a putative autoinhibitory domain (AID) and a C-terminal region required for beta subunit binding. The beta scaffolding subunit mediates AMPK assembly by bridging alpha and gamma subunits. The C-terminal domain of the AMPK alpha 1 subunit interacts with the C-terminal region of the beta subunit to form a tight alpha-beta complex that is associated with the gamma subunit. The AMPK alpha subunit auto-inhibitory region interacts with the kinase domain; this inhibition is negated by the interaction with the AMPK gamma subunit [].AMPK has been implicated in a number of diseases related to energy metabolism including type 2 diabetes, obesity and cancer [, ]. AMPK is activated by rising AMP concentrations coupled with falling ATP concentrations. Activation of AMPK is also dependent on the phosphorylation of alpha subunit by upstream kinases such as LKB1 [].Vertebrates contain two isoforms of the alpha subunit, alpha1 and alpha2, which are encoded by different genes, PRKAA1 and PRKAA2, respectively, and show varying expression patterns. AMPKalpha2 shows cytoplasmic and nuclear localization, whereas AMPKalpha1 is localized only in the cytoplasm [, ].
AMPK, a serine/threonine protein kinase (STK), catalyzes the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. It acts as a sensor for the energy status of the cell and is activated by cellular stresses that lead to ATP depletion such as hypoxia, heat shock, and glucose deprivation, among others. AMPK is a heterotrimer of three subunits: alpha, beta, and gamma []. The alpha subunit is the catalytic subunit and it contains an N-terminal kinase domain, a putative autoinhibitory domain (AID) and a C-terminal region required for beta subunit binding. The beta scaffolding subunit mediates AMPK assembly by bridging alpha and gamma subunits. The C-terminal domain of the AMPK alpha 1 subunit interacts with the C-terminal region of the beta subunit to form a tightalpha-beta complex that is associated with the gamma subunit. The AMPK alpha subunit auto-inhibitory region interacts with the kinase domain; this inhibition is negated by the interaction with the AMPK gamma subunit [].AMPK has been implicated in a number of diseases related to energy metabolism including type 2 diabetes, obesity and cancer [, ]. AMPK is activated by rising AMP concentrations coupled with falling ATP concentrations. Activation of AMPK is also dependent on the phosphorylation of alpha subunit by upstream kinases such as LKB1 [].Vertebrates contain two isoforms of the alpha subunit, alpha1 and alpha2, which are encoded by different genes, PRKAA1 and PRKAA2, respectively, and show varying expression patterns. AMPKalpha1 is the predominant isoform expressed in bone; it plays a role in bone remodeling in response to hormonal regulation []. AMPK alpha1 impacts the regulation of fat metabolism []. It also mediates the vasoprotective effects of estrogen through phosphorylation of another in vivo substrate, RhoA [].
