ArticleCellular signalling2018
A cellular threshold for active ERK1/2 levels determines Raf/MEK/ERK-mediated growth arrest versus death responses.
Article in Cellular signalling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 32 citations in OpenAlex.
- Variant-Specific Landscape of Mutual Exclusivity Among BRAF, EGFR, and KRAS Oncogenes Reveals Overlap With Functionally Antagonistic Mutant Pairs.International journal of cancer · 2026Article
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- Bicaudal‑C1 in Cancer: Molecular Mechanisms and Therapeutic Strategies Integrating Chinese and Western Medicine.Drug design, development and therapy · 2026Review
- Changes of Sonic Hedgehog mediated FAK/ERK pathway proteins in amyotrophic lateral sclerosis model mice.Psychopharmacology · 2026Article
- SCAMP3-Driven Regulation of ERK1/2 and Autophagy Phosphoproteomics Signatures in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Article
- Erk1Oncogene · 2025Article
- ERK1/2 interaction with DHPS regulates eIF5A deoxyhypusination independently of ERK kinase activity.Cell reports · 2024Article
- Interdependency and differential expression of ERK1 and ERK2 in breast and melanoma cell lines.Journal of the Egyptian National Cancer Institute · 2024Article
- FGL2/FcγRIIB Signalling Mediates Arterial Shear Stress-Mediated Endothelial Cell Apoptosis: Implications for Coronary Artery Bypass Vein Graft Pathogenesis.International journal of molecular sciences · 2024Article
- Context-dependent roles for ubiquitous mitochondrial creatine kinase CKMT1 in breast cancer progression.Cell reports · 2024Article
- ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework.NPJ precision oncology · 2024Review
- Review
- Article
- Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy.Molecular biomedicine · 2022Review
- Article
- Specificity of CD200/CD200R pathway in LPS-induced lung inflammation.Frontiers in immunology · 2022Article
- Echinacoside Induces Mitochondria-Mediated Pyroptosis through Raf/MEK/ERK Signaling in Non-Small Cell Lung Cancer Cells.Journal of immunology research · 2022Article
- eIF5A-Independent Role of DHPS in p21International journal of molecular sciences · 2021Article
- Article
- ERK: A Double-Edged Sword in Cancer. ERK-Dependent Apoptosis as a Potential Therapeutic Strategy for Cancer.Cells · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In addition to its conventional role for cell proliferation and survival, the Raf/MEK/Extracellular signal-regulated kinase (ERK) pathway can also induce growth arrest and death responses, if aberrantly activated. Here, we determined a molecular basis of ERK1/2 signaling that underlies these growth inhibitory physiological outputs. We found that overexpression of ERK1 or ERK2 switches ΔRaf-1:ER-induced growth arrest responses to caspase-dependent apoptotic death responses in different cell types. These death responses, however, were reverted to growth arrest responses upon titration of cellular phospho-ERK1/2 levels by the MEK1/2 inhibitor AZD6244. These data suggest that a cellular threshold for active ERK1/2 levels exists and affects the cell fate between death and growth arrest. We also found that death-mediating ability of ERK2 is abolished by the catalytic site-disabling Lys52Arg replacement or significantly attenuated by the F-site recruitment site-disabling Tyr261Asn replacement, although unaffected by the mutations that disable the common docking groove or the dimerization interface. Therefore, ERK1/2 mediates death signaling dependently of kinase activity and specific physical interactions. Intriguingly, Tyr261Asn-replaced ERK2 could still mediate growth arrest signaling, further contrasting the molecular basis of ERK1/2-mediated growth arrest and death signaling. These data reveal a mechanism underlying the role of ERK1/2 as a focal point of Raf/MEK/ERK-mediated growth arrest and death signaling.
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.