ATP sensitive bi-quinoline activator of the AMP-activated protein kinase
John W Scott, Jonathan S Oakhill, Naomi XY Ling, Christopher G Langendorf, Richard C Foitzik, Bruce E Kemp, Olaf-Georg Issinger
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2014
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 αβγ isoforms in vitro except complexes containing the γ3 subunit. JJO-1 does not directly activate the autoinhibited α 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 γ subun..View full abstract
Awarded by Danish Cancer Society
This study was supported by grants from the Australian Research Council and National Health and Medical Research Council, the Australian Government Co-Operative Research Centre's (CRC) Initiative, and the Victorian Government Operational Infrastructure Support Scheme. BEK is an NHMRC Research Fellow and JSO an ARC Future Fellow. OGI received a travel grant from the Danish Cancer Society (No. DR08055).