AMP-activated protein kinase in metabolic control and insulin signaling.
Article Details
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Towler MC, Hardie DG
AMP-activated protein kinase in metabolic control and insulin signaling.
Circ Res. 2007 Feb 16;100(3):328-41.
- PubMed ID
- 17307971 [ View in PubMed]
- Abstract
The AMP-activated protein kinase (AMPK) system acts as a sensor of cellular energy status that is conserved in all eukaryotic cells. It is activated by increases in the cellular AMP:ATP ratio caused by metabolic stresses that either interfere with ATP production (eg, deprivation for glucose or oxygen) or that accelerate ATP consumption (eg, muscle contraction). Activation in response to increases in AMP involves phosphorylation by an upstream kinase, the tumor suppressor LKB1. In certain cells (eg, neurones, endothelial cells, and lymphocytes), AMPK can also be activated by a Ca(2+)-dependent and AMP-independent process involving phosphorylation by an alternate upstream kinase, CaMKKbeta. Once activated, AMPK switches on catabolic pathways that generate ATP, while switching off ATP-consuming processes such as biosynthesis and cell growth and proliferation. The AMPK complex contains 3 subunits, with the alpha subunit being catalytic, the beta subunit containing a glycogen-sensing domain, and the gamma subunits containing 2 regulatory sites that bind the activating and inhibitory nucleotides AMP and ATP. Although it may have evolved to respond to metabolic stress at the cellular level, hormones and cytokines such as insulin, leptin, and adiponectin can interact with the system, and it now appears to play a key role in maintaining energy balance at the whole body level. The AMPK system may be partly responsible for the health benefits of exercise and is the target for the antidiabetic drug metformin. It is a key player in the development of new treatments for obesity, type 2 diabetes, and the metabolic syndrome.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Metformin 5'-AMP-activated protein kinase subunit beta-1 Protein Humans YesInducerActivatorDetails - Polypeptides
Name UniProt ID 5'-AMP-activated protein kinase subunit beta-1 Q9Y478 Details 5'-AMP-activated protein kinase catalytic subunit alpha-1 Q13131 Details 5'-AMP-activated protein kinase subunit beta-2 O43741 Details 5'-AMP-activated protein kinase catalytic subunit alpha-2 P54646 Details 5'-AMP-activated protein kinase subunit gamma-1 P54619 Details 5'-AMP-activated protein kinase subunit gamma-2 Q9UGJ0 Details 5'-AMP-activated protein kinase subunit gamma-3 Q9UGI9 Details