ArticleMolecular bioSystems2013
Exploring higher-order EGFR oligomerisation and phosphorylation--a combined experimental and theoretical approach.
Article in Molecular bioSystems, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- VEGFR2 dimerization kinetics on the cell surface determined by microscopy and mathematical modeling.Biophysical journal · 2026Article
- Differential ErbB receptor dimerization modulates the ability of EGF receptor ligands to regulate metabolic flux.The Journal of biological chemistry · 2026Article
- Tetraspanin CD82 shapes EGFR signaling outcomes through nanoscale receptor organization.The Journal of cell biology · 2026Article
- Spatial and stoichiometric in situ analysis of biomolecular oligomerization at single-protein resolution.Nature communications · 2025Article
- Mathematical Modeling and Inference of Epidermal Growth Factor-Induced Mitogen-Activated Protein Kinase Cell Signaling Pathways.International journal of molecular sciences · 2024Review
- Drug-resistant EGFR mutations promote lung cancer by stabilizing interfaces in ligand-free kinase-active EGFR oligomers.Nature communications · 2024Article
- Surface-Patterned DNA Origami Rulers Reveal Nanoscale Distance Dependency of the Epidermal Growth Factor Receptor Activation.Nano letters · 2024Article
- Distinct interactions stabilize EGFR dimers and higher-order oligomers in cell membranes.Cell reports · 2024Article
- The dependence of EGFR oligomerization on environment and structure: A camera-based N&B study.Biophysical journal · 2022Article
- NF-kB in Signaling Patterns and Its Temporal Dynamics Encode/Decode Human Diseases.Life (Basel, Switzerland) · 2022Review
- Multivalent Ligand-Nanoparticle Conjugates Amplify Reactive Oxygen Species Second Messenger Generation and Enhance Epidermal Growth Factor Receptor Phosphorylation.Bioconjugate chemistry · 2022Article
- Critical roles for EGFR and EGFR-HER2 clusters in EGF binding of SW620 human carcinoma cells.Journal of the Royal Society, Interface · 2022Article
- Competitive binding of STATs to receptor phospho-Tyr motifs accounts for altered cytokine responses.eLife · 2021Article
- Molecular Targeting of Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR).Molecules (Basel, Switzerland) · 2021Review
- Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy.Biomolecules · 2020Review
- Homo-Oligomerisation in Signal Transduction: Dynamics, Homeostasis, Ultrasensitivity, Bistability.Journal of theoretical biology · 2020Article
- Bayesian inference using qualitative observations of underlying continuous variables.Bioinformatics (Oxford, England) · 2020Article
- Dissecting Particle Uptake Heterogeneity in a Cell Population Using Bayesian Analysis.Biophysical journal · 2020Article
- Receptor tyrosine kinase activation: From the ligand perspective.Current opinion in cell biology · 2020Review
- Membrane receptor activation mechanisms and transmembrane peptide tools to elucidate them.The Journal of biological chemistry · 2020Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The epidermal growth factor receptor (EGFR) kinase is generally considered to be activated by either ligand-induced dimerisation or a ligand-induced conformational change within pre-formed dimers. Ligand-induced higher-order EGFR oligomerisation or clustering has been reported but it is not clear how EGFR oligomers, as distinct from EGFR dimers, influence signaling outputs. To address this question, we combined measures of receptor clustering (microscopy; image correlation spectroscopy) and phosphorylation (Western blots) with modelling of mass-action chemical kinetics. A stable BaF/3 cell-line that contains a high proportion (>90%) of inactive dimers of EGFR-eGFP but no secreted ligand and no other detectable ErbB receptors was used as the model cell system. EGF at concentrations of greater than 1 nM was found to cluster EGFR-eGFP dimers into higher-order complexes and cause parallel increases in EGFR phosphorylation. The kinetics of EGFR clustering and phosphorylation were both rapid, plateauing within 2 minutes after stimulation with 30 nM EGF. A rule-based model was formulated to interpret the data. This model took into account ligand binding, ligand-induced conformational changes in the cytosolic tail, monomer-dimer-trimer-tetramer transitions via ectodomain- and kinase-mediated interactions, and phosphorylation. The model predicts that cyclic EGFR tetramers are the predominant phosphorylated species, in which activated receptor dimers adopt a cyclic side-by-side orientation, and that receptor kinase activation is stabilised by the intramolecular interactions responsible for cyclic tetramerization.
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Registered trials
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