ReviewBiophysical journal2019
Emerging Allosteric Mechanism of EGFR Activation in Physiological and Pathological Contexts.
Review in Biophysical journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 44 citations in OpenAlex.
- Imidazole-[1,5‑ACS omega · 2026Article
- Fibroblast EGFR signaling mediates ricin toxin-induced acute lung injury via EGR1/CXCL1 axis.Archives of toxicology · 2025Article
- Drug resistance and tumor heterogeneity: cells and ensembles.Biophysical reviews · 2025Review
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- Advancing Molecular Simulations: Merging Physical Models, Experiments, and AI to Tackle Multiscale Complexity.The journal of physical chemistry letters · 2025Review
- Allosteric ligand-driven smart nanoconjugates for mutation-selective EGFR targeting: A precision approach to overcoming tyrosine kinase inhibitor resistance.BioImpacts : BI · 2025Review
- Targeting the epidermal growth factor receptor (EGFR/ErbB) for the potential treatment of renal pathologies.Frontiers in pharmacology · 2024Review
- Review
- Phenotypic heterogeneity in human genetic diseases: ultrasensitivity-mediated threshold effects as a unifying molecular mechanism.Journal of biomedical science · 2023Review
- Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance.Japanese journal of clinical oncology · 2023Review
- Allele-specific activation, enzyme kinetics, and inhibitor sensitivities of EGFR exon 19 deletion mutations in lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Emerging strategies to overcome resistance to third-generation EGFR inhibitors.Journal of hematology & oncology · 2022Review
- Mechanism of activation and the rewired network: New drug design concepts.Medicinal research reviews · 2022Review
- Structural Insight and Development of EGFR Tyrosine Kinase Inhibitors.Molecules (Basel, Switzerland) · 2022Review
- Unlocking phenotypic plasticity provides novel insights for immunity and personalized therapy in lung adenocarcinoma.Frontiers in genetics · 2022Article
- Macrophages-induced IL-18-mediated eosinophilia promotes characteristics of pancreatic malignancy.Life science alliance · 2021Article
- Updated Insights on EGFR Signaling Pathways in Glioma.International journal of molecular sciences · 2021Review
- Receptor tyrosine kinase ligands and inflammatory cytokines cooperatively suppress the fibrogenic activity in temporomandibular-joint-derived fibroblast-like synoviocytes via mitogen-activated protein kinase kinase/extracellular signal-regulated kinase.Experimental and therapeutic medicine · 2020Article
- New analysis pipeline for high-throughput domain-peptide affinity experiments improves SH2 interaction data.The Journal of biological chemistry · 2020Article
- Advances in targeting EGFR allosteric site as anti-NSCLC therapy to overcome the drug resistance.Pharmacological reports : PR · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Protein kinases are key players in signal transduction pathways where they are crafted into two functional states. In response to growth factor binding stimulus, epidermal growth factor receptor (EGFR), which is physiologically populated in an autoinhibited inactive state, becomes active. Here, we outline a simple allostery scheme to clarify how an extracellular (ligand-dependent) binding event activates the intracellular EGFR kinase domain via (dimer-dependent) asymmetric dimerization, as well as how pathologically overexpressed EGFR or constitutively active mutants, leads to oncogenic pathway activation. Our underlying allosteric activation mechanism derives from a collection of inactive versus active EGFR structural, biochemical (negatively cooperative ligand binding), and biophysical (weak coupling between extracellular and intracellular kinase dimerization) data. The emerging structural insight reveals that ligand-dependent physiological activation is an outside-in allosteric activation with strong structural coupling across the membrane. In contrast, ligand-independent pathological activation is a weak inside-out activation mediated by intracellular kinase dimerization, which is structurally accommodated by additional extracellular dimers.
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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.