AMP-activated protein kinase - An archetypal protein kinase cascade?

✍ Scribed by D. Grahame Hardie; Robert W. Mackintosh

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 724 KB
• Volume: 14
• Category: Article
• ISSN: 0265-9247
• DOI: 10.1002/bies.950141011

✦ Synopsis

Mammalian AMP-activated protein kinase is the central component of a protein kinase cascade which inactivates three key enzymes involvcd 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 thcrefore 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.

Physiological Targets for the AMP-activated Protein Kinase

The known physiological targets for the kinase. and their functions, are summarised in Figure 2. In addition to acetyl-CoA carboxylase and HMG-CoA reductase, the kinase also phosphorylates hormone-senritive lipasekholesterol