Journal article
β-Subunit myristoylation is the gatekeeper for initiating metabolic stress sensing by AMP-activated protein kinase (AMPK)
JS Oakhill, ZP Chen, JW Scott, R Steel, LA Castelli, N Linga, SL Macaulay, BE Kemp
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2010
Abstract
The AMP-activated protein kinase (AMPK) is an α-βγ heterotrimer that acts as a master metabolic regulator to maintain cellular energy balance following increased energy demand and increases in the AMP/ATP ratio. This regulation provides dynamic control of energy metabolism, matching energy supply with demand that is essential for the function and survival of organisms. AMPK is inactive unless phosphorylated on Thr172 in the α-catalytic subunit activation loop by upstream kinases (LKB1 or calcium-calmodulindependent protein kinase kinase β). How a rise in AMP levels triggers AMPK α-Thr172 phosphorylation and activation is incompletely understood. Here we demonstrate unequivocally that AMP dir..
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Funding Acknowledgements
We thank F. Katsis for antibody preparation, J. Gordon (Washington University, St. Louis) for N-myristoyl transferase, N. Birnberg (Mercury Therapeutics, Inc.) for LKB1, and A. Means (Duke University Medical Center, NC) for partial CaMKK beta constructs. This work was supported by grants from the Australian Research Council and the National Health and Medical Research Council (NHMRC). B.E.K. is an NHMRC Fellow.