ATP sensitive bi-quinoline activator of the AMP-activated protein kinase

John W Scott, Jonathan S Oakhill, Naomi X Y Ling, Christopher Grant Langendorf, Richard Foitzik, Bruce Ernest Kemp, Olaf-Georg Issinger

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

The AMP-activated protein kinase (AMPK) regulates cellular and whole-body energy balance in response to changes in adenylate charge and hormonal signals. Activation of AMPK in tissues such as skeletal muscle and liver reverses many of the metabolic defects associated with obesity and Type 2 diabetes. Here we report a bi-quinoline (JJO-1) that allosterically activates all AMPK a?? isoforms in vitro except complexes containing the ?3 subunit. JJO-1 does not directly activate the autoinhibited a subunit kinase domain and differs among other known direct activators of AMPK in that allosteric activation occurs only at low ATP concentrations, and is not influenced by either mutation of the ? subunit adenylate-nucleotide binding sites or deletion of the ? subunit carbohydrate-binding module. Our findings indicate that AMPK has multiple modes of allosteric activation that may be exploited to design isoform-specific activators as potential therapeutics for metabolic diseases.
Original languageEnglish
Pages (from-to)435 - 440
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume443
Issue number2
DOIs
Publication statusPublished - 2014

Cite this

Scott, J. W., Oakhill, J. S., Ling, N. X. Y., Langendorf, C. G., Foitzik, R., Kemp, B. E., & Issinger, O-G. (2014). ATP sensitive bi-quinoline activator of the AMP-activated protein kinase. Biochemical and Biophysical Research Communications, 443(2), 435 - 440. https://doi.org/10.1016/j.bbrc.2013.11.130
Scott, John W ; Oakhill, Jonathan S ; Ling, Naomi X Y ; Langendorf, Christopher Grant ; Foitzik, Richard ; Kemp, Bruce Ernest ; Issinger, Olaf-Georg. / ATP sensitive bi-quinoline activator of the AMP-activated protein kinase. In: Biochemical and Biophysical Research Communications. 2014 ; Vol. 443, No. 2. pp. 435 - 440.
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Scott, JW, Oakhill, JS, Ling, NXY, Langendorf, CG, Foitzik, R, Kemp, BE & Issinger, O-G 2014, 'ATP sensitive bi-quinoline activator of the AMP-activated protein kinase', Biochemical and Biophysical Research Communications, vol. 443, no. 2, pp. 435 - 440. https://doi.org/10.1016/j.bbrc.2013.11.130

ATP sensitive bi-quinoline activator of the AMP-activated protein kinase. / Scott, John W; Oakhill, Jonathan S; Ling, Naomi X Y; Langendorf, Christopher Grant; Foitzik, Richard; Kemp, Bruce Ernest; Issinger, Olaf-Georg.

In: Biochemical and Biophysical Research Communications, Vol. 443, No. 2, 2014, p. 435 - 440.

Research output: Contribution to journalArticleResearchpeer-review

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