ArticleThe Journal of physiology2009
A Ca(2+)-calmodulin-eEF2K-eEF2 signalling cascade, but not AMPK, contributes to the suppression of skeletal muscle protein synthesis during contractions.
Article in The Journal of physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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.
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.
Who cites it
45 citing papers in PubMed, 106 citations in OpenAlex.
- Intensive training and reduced volume increases muscle FXYD1 expression and phosphorylation at rest and during exercise in athletes.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Trial
- Protein ingestion does not impair exercise-induced AMPK signalling when in a glycogen-depleted state: implications for train-low compete-high.European journal of applied physiology · 2013Trial
- Training in the fasted state facilitates re-activation of eEF2 activity during recovery from endurance exercise.European journal of applied physiology · 2011Trial
- Farm animal evolution demonstrates hidden molecular basis of human traits.bioRxiv : the preprint server for biology · 2026Article
- Neural stimulation suppresses mTORC1-mediated protein synthesis in skeletal muscle.Science advances · 2025Article
- Endurance exercise with reduced muscle glycogen content influences substrate utilization and attenuates acute mTORC1- and autophagic signaling in human type I and type II muscle fibers.Skeletal muscle · 2025Article
- PPP2CA Inhibition Promotes Ferroptosis Sensitivity Through AMPK/SCD1 Pathway in Colorectal Cancer.Digestive diseases and sciences · 2024Article
- Characterisation of the Muscle Protein Synthetic Response to Resistance Exercise in Healthy Adults: A Systematic Review and Exploratory Meta-Analysis.Translational sports medicine · 2024Review
- Investigating Eukaryotic Elongation Factor 2 Kinase/Eukaryotic Translation Elongation Factor 2 Pathway Regulation and Its Role in Protein Synthesis Impairment during Disuse-Induced Skeletal Muscle Atrophy.The American journal of pathology · 2023Article
- ADP enhances the allosteric activation of eukaryotic elongation factor 2 kinase by calmodulin.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- eEF2 improves dense connective tissue repair and healing outcome by regulating cellular death, autophagy, apoptosis, proliferation and migration.Cellular and molecular life sciences : CMLS · 2023Article
- Ubiquitin-proteasome pathway in skeletal muscle atrophy.Frontiers in physiology · 2023Review
- Protein signalling in response to ex vivo dynamic contractions is independent of training status in rat skeletal muscle.Experimental physiology · 2022Article
- Liver alanine catabolism promotes skeletal muscle atrophy and hyperglycaemia in type 2 diabetes.Nature metabolism · 2021Article
- Synergistic antitumor effect of resveratrol and sorafenib on hepatocellular carcinoma through PKA/AMPK/eEF2K pathway.Food & nutrition research · 2021Article
- Insights Into the Pathologic Roles and Regulation of Eukaryotic Elongation Factor-2 Kinase.Frontiers in molecular biosciences · 2021Review
- How Postural Muscle Senses Disuse? Early Signs and Signals.International journal of molecular sciences · 2020Review
- Molecular regulation of human skeletal muscle protein synthesis in response to exercise and nutrients: a compass for overcoming age-related anabolic resistance.American journal of physiology. Cell physiology · 2019Review
- The Role of AMPK in the Regulation of Skeletal Muscle Size, Hypertrophy, and Regeneration.International journal of molecular sciences · 2018Review
- Cross-talk between protein synthesis, energy metabolism and autophagy in cancer.Current opinion in genetics & development · 2018Review
Corrections and comments
- Commented on by
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Skeletal muscle protein synthesis rate decreases during contractions but the underlying regulatory mechanisms are poorly understood. It was hypothesized that there would be a coordinated regulation of eukaryotic elongation factor 2 (eEF2) and eukaryotic initiation factor 4E-binding protein 1 (4EBP1) phosphorylation by signalling cascades downstream of rises in intracellular [Ca(2+)] and decreased energy charge via AMP-activated protein kinase (AMPK) in contracting skeletal muscle. When fast-twitch skeletal muscles were contracted ex vivo using different protocols, the suppression of protein synthesis correlated more closely with changes in eEF2 than 4EBP1 phosphorylation. Using a combination of Ca(2+) release agents and ATPase inhibitors it was shown that the 60-70% suppression of fast-twitch skeletal muscle protein synthesis during contraction was equally distributed between Ca(2+) and energy turnover-related mechanisms. Furthermore, eEF2 kinase (eEF2K) inhibition completely blunted increases in eEF2 phosphorylation and partially blunted (i.e. 30-40%) the suppression of protein synthesis during contractions. The 3- to 5-fold increase in skeletal muscle eEF2 phosphorylation during contractions in situ was rapid and sustained and restricted to working muscle. The increase in eEF2 phosphorylation and eEF2K activation were downstream of Ca(2+)-calmodulin (CaM) but not other putative activating factors such as a fall in intracellular pH or phosphorylation by protein kinases. Furthermore, blunted protein synthesis and 4EBP1 dephosphorylation were unrelated to AMPK activity during contractions, which was exemplified by normal blunting of protein synthesis during contractions in muscles overexpressing kinase-dead AMPK. In summary, in fast-twitch skeletal muscle, the inhibition of eEF2 activity by phosphorylation downstream of Ca(2+)-CaM-eEF2K signalling partially contributes to the suppression of protein synthesis during exercise/contractions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.