Evidence map›Paper›PMID 22114351›Full record

ArticleMolecular biology of the cell2012

AMPK directly inhibits NDPK through a phosphoserine switch to maintain cellular homeostasis.

Rob U Onyenwoke, Lawrence J Forsberg, Lucy Liu, Tyisha Williams, Oscar Alzate, Jay E Brenman

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

21 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. The actions of NME1/NDPK-A and NME2/NDPK-B as protein kinases.Laboratory investigation; a journal of technical methods and pathology · 2018
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Colon cancer-associated mutator DNA polymerase δ variant causes expansion of dNTP pools increasing its own infidelity.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  13. Nucleoside diphosphate kinases (NDPKs) in animal development.Cellular and molecular life sciences : CMLS · 2015
    Review
  14. Article
  15. Article
  16. Lysosomal Storage Diseases-Regulating Neurodegeneration.Journal of experimental neuroscience · 2015
    Review
  17. Article
  18. AMPK as a potential anticancer target - friend or foe?Current pharmaceutical design · 2014
    Review
  19. Article
  20. Article
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

6 authors at 1 institution in 1 country.

Rob U OnyenwokeNeuroscience Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Lawrence J Forsberg
Lucy Liu
Tyisha Williams
Oscar Alzate
Jay E Brenman
University of North Carolina at Chapel Hill · US

Funding

Integrated Training in Cancer Model SystemsT32CA009156 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 1985 to 2020
$19.7M
Genetic Elucidation of AMP-Activated Protein Kinase Signaling MechanismsR01NS080108 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BRENMAN, JAY · 2012 to 2016
$1.6M
HTS assay development to identify regulators of peroxisome biogenesis/functionR21NS063858 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BRENMAN, JAY, SEXTON, JONATHAN ZACHARY · 2009 to 2009
$155k
NCI NIH HHS 5-T32-CA09156-35NCI NIH HHS T32 CA009156NINDS NIH HHS R01NS063858NINDS NIH HHS R01 NS080108NINDS NIH HHS R21 NS063858
6 · The paper itself

Abstract

AMP-activated protein kinase (AMPK) is a key energy sensor that regulates metabolism to maintain cellular energy balance. AMPK activation has also been proposed to mimic benefits of caloric restriction and exercise. Therefore, identifying downstream AMPK targets could elucidate new mechanisms for maintaining cellular energy homeostasis. We identified the phosphotransferase nucleoside diphosphate kinase (NDPK), which maintains pools of nucleotides, as a direct AMPK target through the use of two-dimensional differential in-gel electrophoresis. Furthermore, we mapped the AMPK/NDPK phosphorylation site (serine 120) as a functionally potent enzymatic "off switch" both in vivo and in vitro. Because ATP is usually the most abundant cellular nucleotide, NDPK would normally consume ATP, whereas AMPK would inhibit NDPK to conserve energy. It is intriguing that serine 120 is mutated in advanced neuroblastoma, which suggests a mechanism by which NDPK in neuroblastoma can no longer be inhibited by AMPK-mediated phosphorylation. This novel placement of AMPK upstream and directly regulating NDPK activity has widespread implications for cellular energy/nucleotide balance, and we demonstrate in vivo that increased NDPK activity leads to susceptibility to energy deprivation-induced death.

Indexed as

HomeostasisAdenosine TriphosphateAmino Acid SequenceAMP-Activated Protein KinasesAnimalsBrainCell Line, TumorDrosophila melanogasterGene Knockout TechniquesHEK293 CellsHumansMaleMiceMice, TransgenicMolecular Sequence DataMutationAdenosine TriphosphateAMP-Activated Protein KinasesNucleoside-Diphosphate KinasePhosphoserine

Identifiers

PMID22114351
PMCPMC3258181
OpenAlexW2128325532

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.