Management of cellular energy by the AMP‐activated protein kinase system

@article{Hardie2003ManagementOC,
  title={Management of cellular energy by the AMP‐activated protein kinase system},
  author={David Grahame Hardie and John W. Scott and David A. Pan and Emma R Hudson},
  journal={FEBS Letters},
  year={2003},
  volume={546}
}
The AMP‐activated protein kinase is a sensor of cellular energy status that is found in all eukaryotic cells. It is activated by rising AMP and falling ATP by a complex mechanism that results in an ultrasensitive response. The functions of the different domains on the three subunits of the αβγ heterotrimer are slowly being unravelled, and a recent development has been the identification of a glycogen‐binding domain on the β subunit. Along with findings that high cellular glycogen represses… 
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Regulation of AMP‐activated protein kinase by a pseudosubstrate sequence on the γ subunit
TLDR
It is proposed that in the absence of AMP this pseudosubstrate sequence binds to the active site groove on the α subunit, preventing phosphorylation by the upstream kinase, LKB1, and access to downstream targets.
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  • D. Hardie
  • Biology, Medicine
    Journal of Cell Science
  • 2004
TLDR
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AMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling
TLDR
Although it may have evolved to respond to metabolic stress at the cellular level, hormones and cytokines such as insulin, leptin, and adiponectin can interact with the system, and it now appears to play a key role in maintaining energy balance at the whole body level.
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TLDR
Findings indicate that AMPK has a pivotal role in regulating pathways that control both energy expenditure and energy intake.
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TLDR
The LKB1→AMPK cascade is switched on by metabolic stresses that either inhibit ATP production or accelerate ATP consumption, and this activates AMPK by a complex and sensitive mechanism involving antagonistic binding of the nucleotides to two sites on the regulatory γ subunits of AMPK.
TRIP6 transcriptional co-activator is a novel substrate of AMP-activated protein kinase.
TLDR
The physical interaction between the catalytic subunit (AMPK-alpha2) of the AMPK complex and TRIP6 in mammalian cells is confirmed by two-hybrid and co-immunoprecipitation assays and evidence that transcriptional co-activator properties of TRIP 6 were enhanced by AMPK action is presented.
AMP-Activated Protein Kinase: A Master Switch in Glucose and Lipid Metabolism
  • D. Hardie
  • Chemistry, Medicine
    Reviews in Endocrine and Metabolic Disorders
  • 2004
TLDR
A fundamental parameter that must be maintained in all living cells is a high ratio of ATP to ADP, which acts as a store of energy analogous to the chemicals in a fully charged battery, and the system that primarily achieves this, the AMP-activated protein kinase cascade, has only become apparent in the last few years.
Nucleotide regulation of AMP-activated protein kinase
TLDR
It seems that AMP binding at Site-1 mediates allostery whilst AMP/ADP binding on Site-3 affords protection against dephosphorylation, and AXP binding constants were used to model binding site occupancies over the concentration ranges used in vitro, and ADP was found to bind more weakly than ADP.
Intracellular signaling of the AMP-activated protein kinase.
TLDR
A better understanding of the AMPK role in intracellular signaling under physiological and pathological conditions may represent a potential strategy for developing therapies for treating many different human diseases and disorders, in which AMPK plays a key role.
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