ArticleMolecular and cellular biology2014
Eukaryotic elongation factor 2 kinase activity is controlled by multiple inputs from oncogenic signaling.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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
54 citing papers in PubMed, 102 citations in OpenAlex.
- Mechanisms and therapeutic opportunities of the ribotoxic stress response in cancer.Molecular oncology · 2026Review
- Distinct signaling mechanisms and proteome phenotypes are elicited by compartment-specific genetic defects of copper homeostasis.bioRxiv : the preprint server for biology · 2026Article
- eEF2K-Mediated Stabilization of PCBP2 Promotes Oncogenic mRNA Programs in Triple-Negative Breast Cancer.International journal of biological sciences · 2026Article
- Systems Biology of Recombinant 2G12 and 353/11 mAb Production in CHO-K1 Cell Lines at Phosphoproteome Level.Proteomes · 2025Article
- Elongation factor 2 in cancer: a promising therapeutic target in protein translation.Cellular & molecular biology letters · 2024Review
- Stress response regulation of mRNA translation: Implications for antioxidant enzyme expression in cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Review
- IRF5 mediates adaptive immunity via altered glutamine metabolism, mTORC1 signaling and post-transcriptional regulation following T cell receptor activation.bioRxiv : the preprint server for biology · 2024Article
- Suppression of eEF2 phosphorylation alleviates synaptic failure and cognitive deficits in mouse models of Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Article
- The autism susceptibility kinase, TAOK2, phosphorylates eEF2 and modulates translation.Science advances · 2024Article
- Review
- Stress-Induced Eukaryotic Translational Regulatory Mechanisms.Journal of clinical and medical sciences · 2024Article
- Review
- Nonsense mutation suppression is enhanced by targeting different stages of the protein synthesis process.PLoS biology · 2023Article
- The central role of translation elongation in response to stress.Biochemical Society transactions · 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
- Impact of silencing eEF2K expression on the malignant properties of chordoma.Molecular biology reports · 2023Article
- Ghrelin rapidly elevates protein synthesis in vitro by employing the rpS6K-eEF2K-eEF2 signalling axis.Cellular and molecular life sciences : CMLS · 2022Article
- Glutamine deficiency in solid tumor cells confers resistance to ribosomal RNA synthesis inhibitors.Nature communications · 2022Article
- eEF2K Activity Determines Synergy to Cotreatment of Cancer Cells With PI3K and MEK Inhibitors.Molecular & cellular proteomics : MCP · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Eukaryotic elongation factor 2 kinase (eEF2K), an atypical calmodulin-dependent protein kinase, phosphorylates and inhibits eEF2, slowing down translation elongation. eEF2K contains an N-terminal catalytic domain, a C-terminal α-helical region and a linker containing several regulatory phosphorylation sites. eEF2K is expressed at high levels in certain cancers, where it may act to help cell survival, e.g., during nutrient starvation. However, it is a negative regulator of protein synthesis and thus cell growth, suggesting that cancer cells may possess mechanisms to inhibit eEF2K under good growth conditions, to allow protein synthesis to proceed. We show here that the mTORC1 pathway and the oncogenic Ras/Raf/MEK/extracellular signal-regulated kinase (ERK) pathway cooperate to restrict eEF2K activity. We identify multiple sites in eEF2K whose phosphorylation is regulated by mTORC1 and/or ERK, including new ones in the linker region. We demonstrate that certain sites are phosphorylated directly by mTOR or ERK. Our data reveal that glycogen synthase kinase 3 signaling also regulates eEF2 phosphorylation. In addition, we show that phosphorylation sites remote from the N-terminal calmodulin-binding motif regulate the phosphorylation of N-terminal sites that control CaM binding. Mutations in the former sites, which occur in cancer cells, cause the activation of eEF2K. eEF2K is thus regulated by a network of oncogenic signaling pathways.
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.