Thienopyridone Drugs Are Selective Activators of AMP-Activated Protein Kinase β1-Containing Complexes

163Citations
Citations of this article
67Readers
Mendeley users who have this article in their library.

Abstract

The AMP-activated protein kinase (AMPK) is an αβγ heterotrimer that plays a pivotal role in regulating cellular and whole-body metabolism. Activation of AMPK reverses many of the metabolic defects associated with obesity and type 2 diabetes, and therefore AMPK is considered a promising target for drugs to treat these diseases. Recently, the thienopyridone A769662 has been reported to directly activate AMPK by an unexpected mechanism. Here we show that A769662 activates AMPK by a mechanism involving the β subunit carbohydrate-binding module and residues from the γ subunit but not the AMP-binding sites. Furthermore, A769662 exclusively activates AMPK heterotrimers containing the β1 subunit. Our findings highlight the regulatory role played by the β subunit in modulating AMPK activity and the possibility of developing isoform specific therapeutic activators of this important metabolic regulator. © 2008 Elsevier Ltd. All rights reserved.

Author supplied keywords

Cite

CITATION STYLE

APA

Scott, J. W., van Denderen, B. J. W., Jorgensen, S. B., Honeyman, J. E., Steinberg, G. R., Oakhill, J. S., … Kemp, B. E. (2008). Thienopyridone Drugs Are Selective Activators of AMP-Activated Protein Kinase β1-Containing Complexes. Chemistry and Biology, 15(11), 1220–1230. https://doi.org/10.1016/j.chembiol.2008.10.005

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free