AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α

Jager, S. and Handschin, C. and St-Pierre, J. and Spiegelman, B. M.. (2007) AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α. Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, H. 29. pp. 12017-12022.

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Official URL: http://edoc.unibas.ch/dok/A5258713

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Activation of AMP-activated kinase (AMPK) in skeletal muscle increases glucose uptake, fatty acid oxidation, and mitochondrial biogenesis by increasing gene expression in these pathways. However, the transcriptional components that are directly targeted by AMPK are still elusive. The peroxisome-proliferator-activated receptor γ coactivator 1α (PGC-1α) has emerged as a master regulator of mitochondrial biogenesis; furthermore, it has been shown that PGC-1α gene expression is induced by exercise and by chemical activation of AMPK in skeletal muscle. Using primary muscle cells and mice deficient in PGC-1α, we found that the effects of AMPK on gene expression of glucose transporter 4, mitochondrial genes, and PGC-1α itself are almost entirely dependent on the function of PGC-1α protein. Furthermore, AMPK phosphorylates PGC-1α directly both in vitro and in cells. These direct phosphorylations of the PGC-1α protein at threonine-177 and serine-538 are required for the PGC-1α-dependent induction of the PGC-1α promoter. These data indicate that AMPK phosphorylation of PGC-1α initiates many of the important gene regulatory functions of AMPK in skeletal muscle.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin)
03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin)
UniBasel Contributors:Handschin, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Dec 2015 10:42
Deposited On:22 Mar 2012 13:20

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