Management of cellular energy by the AMP-activated protein kinase system.
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 alphabetagamma heterotrimer are slowly being unravelled, and a recent development has been the identification of a glycogen-binding domain on the beta 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.
Hardie
D Grahame
DG
Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, UK. d.g.hardie@dundee.ac.uk
Scott
John W
JW
Pan
David A
DA
Hudson
Emma R
ER
D000249:Adenosine Monophosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D004734:Energy Metabolism; D004789:Enzyme Activation; D005057:Eukaryotic Cells; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D020033:Protein Isoforms; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D017386:Sequence Homology, Amino Acid
D020033:Protein Isoforms; D021122:Protein Subunits; D000249:Adenosine Monophosphate; D006003:Glycogen; D011494:Protein Kinases