Journal article

The Ancient Drug Salicylate Directly Activates AMP-Activated Protein Kinase

Simon A Hawley, Morgan D Fullerton, Fiona A Ross, Jonathan D Schertzer, Cyrille Chevtzoff, Katherine J Walker, Mark W Peggie, Darya Zibrova, Kevin A Green, Kirsty J Mustard, Bruce E Kemp, Kei Sakamoto, Gregory R Steinberg, D Grahame Hardie



Salicylate, a plant product, has been in medicinal use since ancient times. More recently, it has been replaced by synthetic derivatives such as aspirin and salsalate, both of which are rapidly broken down to salicylate in vivo. At concentrations reached in plasma after administration of salsalate or of aspirin at high doses, salicylate activates adenosine monophosphate-activated protein kinase (AMPK), a central regulator of cell growth and metabolism. Salicylate binds at the same site as the synthetic activator A-769662 to cause allosteric activation and inhibition of dephosphorylation of the activating phosphorylation site, threonine-172. In AMPK knockout mice, effects of salicylate to inc..

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Awarded by Wellcome Trust

Awarded by Medical Research Council

Awarded by MRC

Funding Acknowledgements

D.G.H. was supported by a Programme Grant (080982) from the Wellcome Trust and K.S. by the Medical Research Council. D.G.H. and K.S. were also funded by the companies (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck Serono, and Pfizer) supporting the Division of Signal Transduction Therapy, Univ. of Dundee. The studies were also supported by grants and fellowship from the Canadian Institutes of Health Research (CIHR) (M.D.F. and G.R.S.), the Canadian Diabetes Association (J.D.S. and G.R.S.), the National Health and Medical Research Council of Australia (G.R.S. and B.E.K.), and the Australian Research Council and the Victorian Government's Operational Infrastructure Support Program (B.E.K.). J.D.S. is a DeGroote Academic Fellow (McMaster Univ.), and M.D.F. a Banting Postdoctoral Fellow (CIHR). G.R.S. is a Canada Research Chair in Metabolism and Obesity.