Management of cellular energy by the AMP‐activated protein kinase system

FEBS Letters

Hardie, D.Grahame¹  Hudson, Emma R¹  Pan, David A¹  Scott, John W¹ 

[1] Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, UK

关键词: AMP-activated protein kinase;    Cellular energy;    ACC1;    acetyl-CoA carboxylase (1/α isoform);    ACC2;    acetyl-CoA carboxylase (2/β isoform);    AICA;    5-aminoimidazole-4-carboxamide;    AMPK;    AMP-activated protein kinase;    CFTR;    cystic fibrosis transmembrane conductance regulator;    eNOS;    endothelial nitric oxide synthase;    KIS;    kinase interaction sequence;    nNOS;    neuronal nitric oxide synthase;    PFK2;    6-phosphofructo-2-kinase;    PI;    phosphatidylinositol;    PPAR-γ;    peroxisome proliferator-activated receptor-γ;   

DOI  :  10.1016/S0014-5793(03)00560-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The AMP-activated protein kinase is a sensor of cellular energy status that is found in all eukaryotic cells. It is activated by rising AMP and falling ATP by a complex mechanism that results in an ultrasensitive response. The functions of the different domains on the three subunits of the αβγ heterotrimer are slowly being unravelled, and a recent development has been the identification of a glycogen-binding domain on the β subunit. Along with findings that high cellular glycogen represses kinase activation, this suggests that the system may be a sensor of glycogen content as well as of AMP and ATP. New insights have been obtained into the sequence and structural features by which the kinase recognises its downstream target proteins, and these are discussed. Once activated by depletion of cellular energy reserves, the kinase switches on ATP-producing catabolic pathways and switches off ATP-consuming processes, both via direct phosphorylation of regulatory proteins and via indirect effects on gene expression. A survey of the range of downstream targets for this important signalling pathway is presented.

【 授权许可】

Unknown