ArticleCell chemical biology2016
Molecular Basis for Redox Activation of Epidermal Growth Factor Receptor Kinase.
Article in Cell chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
What it found
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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.
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Who cites it
81 citing papers in PubMed, 136 citations in OpenAlex.
- In Pursuit of Enduring Inactivation: A Perspective on the Development and Study of Irreversible-Covalent Inhibitors.Biochemistry · 2026Review
- Possible Links Between PMInternational journal of molecular sciences · 2026Review
- Nitration in cancer signaling.Redox biology · 2026Review
- Redox regulation of EGFR activation by thioredoxin reductase 3 drives resistance to EGFR inhibitors in triple-negative breast cancer.Cell death discovery · 2026Article
- Defining and refining the cysteine redoxome through sulfur chemical biology.Nature chemical biology · 2026Review
- Cysteine addiction in drug resistant glioblastoma and therapeutic targeting with designer selenium compounds.Neuro-oncology · 2026Article
- Chemical Proteomics Reveals Regulation of Bile Salt Hydrolases via Oxidative Post-translational Modifications.Journal of the American Chemical Society · 2026Article
- Pervanadate-induced oxidation relieves autoinhibition of the protein tyrosine kinase SRC.Science signaling · 2026Article
- Chemical proteomics reveals regulation of bile salt hydrolases via oxidative post-translational modifications.bioRxiv : the preprint server for biology · 2025Article
- Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Redox Regulation of cAMP-Dependent Protein Kinase and Its Role in Health and Disease.Life (Basel, Switzerland) · 2025Review
- Article
- Ferroptosis - a potential feature underlying neratinib-induced colonic epithelial injury.Cancer chemotherapy and pharmacology · 2024Article
- Fundamentals of redox regulation in biology.Nature reviews. Molecular cell biology · 2024Review
- Cysteine sulfenylation contributes to liver fibrosis via the regulation of EphB2-mediated signaling.Cell death & disease · 2024Article
- Redox takes control.eLife · 2024Article
- Redox Regulation of Brain Selective Kinases BRSK1/2: Implications for Dynamic Control of the Eukaryotic AMPK family through Cys-based mechanisms.bioRxiv : the preprint server for biology · 2024Article
- RedOx regulation of LRRK2 kinase activity by active site cysteines.NPJ Parkinson's disease · 2024Article
- The Acute, Short-, and Long-Term Effects of Endurance Exercise on Skeletal Muscle Transcriptome Profiles.International journal of molecular sciences · 2024Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) is a target of signal-derived H2O2, and oxidation of active-site cysteine 797 to sulfenic acid enhances kinase activity. Although a major class of covalent drugs targets C797, nothing is known about its catalytic importance or how S-sulfenylation leads to activation. Here, we report the first detailed functional analysis of C797. In contrast to prior assumptions, mutation of C797 diminishes catalytic efficiency in vitro and cells. The experimentally determined pKa and reactivity of C797 toward H2O2 correspondingly distinguish this residue from the bulk of the cysteinome. Molecular dynamics simulation of reduced versus oxidized EGFR, reinforced by experimental testing, indicates that sulfenylation of C797 allows new electrostatic interactions to be formed with the catalytic loop. Finally, we show that chronic oxidative stress yields an EGFR subpopulation that is refractory to the FDA-approved drug afatinib. Collectively, our data highlight the significance of redox biology to understanding kinase regulation and drug pharmacology.
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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.