AMP-activated protein kinase--an archetypal protein kinase cascade?
Mammalian AMP-activated protein kinase is the central component of a protein kinase cascade which inactivates three key enzymes involved in the synthesis or release of free fatty acids and cholesterol inside the cell. The kinase cascade is activated by elevation of AMP, and perhaps also by fatty acid and cholesterol metabolites. The system may fulfil a protective function, preventing damage caused by depletion of ATP or excessive intracellular release of free lipids, a type of stress response. Recent evidence suggests that it may have been in existence for at least a billion years, since a very similar protein kinase cascade is present in higher plants. This system therefore represents an early eukaryotic protein kinase cascade, which is unique in that it is regulated by intracellular metabolites rather than extracellular signals or cell cycle events.
Hardie
D G
DG
Biochemistry Department, University, Dundee, Scotland, UK.
MacKintosh
R W
RW
D055372:AMP-Activated Protein Kinases; D000249:Adenosine Monophosphate / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002784:Cholesterol / Q000378:metabolism; D002940:Circadian Rhythm; D005227:Fatty Acids / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008099:Liver / Q000201:enzymology; D008322:Mammals / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D010940:Plant Proteins / Q000737:chemistry; D011494:Protein Kinases / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases; D011817:Rabbits; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D005227:Fatty Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009097:Multienzyme Complexes; D010940:Plant Proteins; D000249:Adenosine Monophosphate; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases