Evidence map›Paper›PMID 20974912›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2010

β-Subunit myristoylation is the gatekeeper for initiating metabolic stress sensing by AMP-activated protein kinase (AMPK).

Jonathan S Oakhill, Zhi-Ping Chen, John W Scott, Rohan Steel, Laura A Castelli, Naomi Ling, S Lance Macaulay, Bruce E Kemp

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers.

0numbers the graph read from it
0cells of the map it votes in
177citing papers in PubMed
9.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

177 citing papers in PubMed, 306 citations in OpenAlex.

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117 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Jonathan S OakhillProtein Chemistry and Metabolism, Saint Vincent's Institute of Medical Research, University of Melbourne, 41 Victoria Parade, Fitzroy 3065, Australia. joakhill@svi.edu.au
Zhi-Ping Chen
John W Scott
Rohan Steel
Laura A Castelli
Naomi Ling
S Lance Macaulay
Bruce E Kemp
St Vincents Institute of Medical Research · AUUniversity of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The AMP-activated protein kinase (AMPK) is an αβγ 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-calmodulin-dependent 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 directly stimulates α-Thr172 phosphorylation provided the AMPK β-subunit is myristoylated. Loss of the myristoyl group abolishes AMP activation and reduces the extent of α-Thr172 phosphorylation. Once AMPK is phosphorylated, AMP further activates allosterically but this activation does not require β-subunit myristoylation. AMP and glucose deprivation also promote membrane association of myristoylated AMPK, indicative of a myristoyl-switch mechanism. Our results show that AMP regulates AMPK activation at the initial phosphorylation step, and that β-subunit myristoylation is important for transducing the metabolic stress signal.

Indexed as

Energy MetabolismAdenosine MonophosphateAllosteric RegulationAMP-Activated Protein KinasesAnimalsCell LineChlorocebus aethiopsCOS CellsGlucoseInsectaMyristic AcidPhosphorylationProtein SubunitsAdenosine MonophosphateAMP-Activated Protein KinasesGlucoseMyristic AcidProtein Subunits

Identifiers

PMID20974912
PMCPMC2984171
OpenAlexW2004814508

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.