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Abstract
Annual Review of Biochemistry
Vol. 67: 821-855 (Volume publication date July 1998)
(doi:10.1146/annurev.biochem.67.1.821)
THE AMP-ACTIVATED/SNF1 PROTEIN KINASE SUBFAMILY: Metabolic Sensors of the Eukaryotic Cell?

D. Grahame Hardie,1 David Carling,2 and Marian Carlson3
1Biochemistry Department, The University, Rundee, DD1 4HN, Scotland, United Kingdom, ;
2MRC Molecular Medicine Group, Imperial College School of Medicine, Hammersmith Hospital, London, W12 0NN, United Kingdom, ;
3Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York 10032; e-mail:

Abstract Mammalian AMP-activated protein kinase and yeast SNF1 protein kinase are the central components of kinase cascades that are highly conserved between animals, fungi, and plants. The AMP-activated protein kinase cascade acts as a metabolic sensor or “fuel gauge” that monitors cellular AMP and ATP levels because it is activated by increases in the AMP:ATP ratio. Once activated, the enzyme switches off ATP-consuming anabolic pathways and switches on ATP-producing catabolic pathways, such as fatty acid oxidation. The SNF1 complex in yeast is activated in response to the stress of glucose deprivation. In this case the intracellular signal or signals have not been identified; however, SNF1 activation is associated with depletion of ATP and elevation of AMP. The SNF1 complex acts primarily by inducing expression of genes required for catabolic pathways that generate glucose, probably by triggering phosphorylation of transcription factors. SNF1-related protein kinases in higher plants are likely to be involved in the response of plant cells to environmental and/or nutritional stress.

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Authors:
D. Grahame Hardie,
David Carling,
Marian Carlson
Keywords:
protein phosphorylation
gene expression
cellular stress
glucose repression
ATP depletion

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