ADP regulates SNF1, the saccharomyces cerevisiae homolog of AMP-activated protein kinase

Mayer, F. V. et al. (2011) ADP regulates SNF1, the saccharomyces cerevisiae homolog of AMP-activated protein kinase. Cell Metabolism, 14(5), pp. 707-714. (doi: 10.1016/j.cmet.2011.09.009) (PMID:22019086) (PMCID:PMC3241989)

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Summary The SNF1 protein kinase complex plays an essential role in regulating gene expression in response to the level of extracellular glucose in budding yeast. SNF1 shares structural and functional similarities with mammalian AMP-activated protein kinase. Both kinases are activated by phosphorylation on a threonine residue within the activation loop segment of the catalytic subunit. Here we show that ADP is the long-sought metabolite that activates SNF1 in response to glucose limitation by protecting the enzyme against dephosphorylation by Glc7, its physiologically relevant protein phosphatase. We also show that the regulatory subunit of SNF1 has two ADP binding sites. The tighter site binds AMP, ADP, and ATP competitively with NADH, whereas the weaker site does not bind NADH, but is responsible for mediating the protective effect of ADP on dephosphorylation. Mutagenesis experiments suggest that the general mechanism by which ADP protects against dephosphorylation is strongly conserved between SNF1 and AMPK.

Item Type:Articles
Additional Information:This study was supported by the Medical Research Council UK (D. Carling and S.J.G.) and grant GM46443 from the National Institutes of Health (M.C.S.)
Glasgow Author(s) Enlighten ID:Leiper, Dr Fiona
Authors: Mayer, F. V., Heath, R., Underwood, E., Sanders, M. J., Carmena, D., McCartney, R. R., Leiper, F. C., Xiao, B., Jing, C., Walker, P. A., Haire, L. F., Ogrodowicz, R., Martin, S. R., Schmidt, M. C., Gamblin, S. J., and Carling, D.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Cell Metabolism
ISSN (Online):1932-7420
Published Online:20 October 2011
Copyright Holders:Copyright © 2011 Elsevier Inc.
First Published:First published in Cell Metabolism 14(5):707-714
Publisher Policy:Reproduced under a Creative Commons License

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