ArticleProceedings of the National Academy of Sciences of the United States of America2004
A structure-based model for ligand binding and dimerization of EGF receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 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.
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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
52 citing papers in PubMed, 125 citations in OpenAlex.
- Mathematical Modeling and Inference of Epidermal Growth Factor-Induced Mitogen-Activated Protein Kinase Cell Signaling Pathways.International journal of molecular sciences · 2024Review
- Cetuximab chemotherapy resistance: Insight into the homeostatic evolution of head and neck cancer (Review).Oncology reports · 2024Review
- Construction of a bacteriophage-derived vector with potential applications in targeted drug delivery and cell imaging.Biotechnology letters · 2024Article
- Epidermal growth factor receptor inhibition potentiates chemotherapeutics-mediated sensitization of metastatic breast cancer stem cells.Cancer reports (Hoboken, N.J.) · 2024Article
- Ligand-induced transmembrane conformational coupling in monomeric EGFR.Nature communications · 2022Article
- Article
- Quantifying the strength of heterointeractions among receptor tyrosine kinases from different subfamilies: Implications for cell signaling.The Journal of biological chemistry · 2020Article
- Novel EGFR ectodomain mutations associated with ligand-independent activation and cetuximab resistance in head and neck cancer.PloS one · 2020Article
- Comprehensive Model for Epidermal Growth Factor Receptor Ligand Binding Involving Conformational States of the Extracellular and the Kinase Domains.Frontiers in cell and developmental biology · 2020Article
- Revisiting a controversy: The effect of EGF on EGFR dimer stability.Biochimica et biophysica acta. Biomembranes · 2020Article
- The RTK Interactome: Overview and Perspective on RTK Heterointeractions.Chemical reviews · 2019Review
- Quantifying the Interaction between EGFR Dimers and Grb2 in Live Cells.Biophysical journal · 2017Article
- Piecing it together: Unraveling the elusive structure-function relationship in single-pass membrane receptors.Biochimica et biophysica acta. Biomembranes · 2017Review
- Rinsing paired-agent model (RPAM) to quantify cell-surface receptor concentrations in topical staining applications of thick tissues.Physics in medicine and biology · 2017Article
- Quantum dots implementation as a label for analysis of early stages of EGF receptor endocytosis: a comparative study on cultured cells.Oncotarget · 2016Article
- Sulfiredoxin Promotes Colorectal Cancer Cell Invasion and Metastasis through a Novel Mechanism of Enhancing EGFR Signaling.Molecular cancer research : MCR · 2015Article
- Quantitative analysis reveals how EGFR activation and downregulation are coupled in normal but not in cancer cells.Nature communications · 2015Article
- The strength and cooperativity of KIT ectodomain contacts determine normal ligand-dependent stimulation or oncogenic activation in cancer.Molecular cell · 2015Article
- Native structure-based modeling and simulation of biomolecular systems per mouse click.BMC bioinformatics · 2014Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
On the basis of the 3D structures of the extracellular ligand-binding domains of the epidermal growth factor (EGF) receptor (EGFR) and ErbB3, a mechanism has been proposed for how the extracellular region of the EGFR is maintained in an autoinhibited configuration and for how EGF binding induces EGFR dimerization and activation. We have attempted to derive a mathematical model for EGF binding to the EGFR and for ligand-induced receptor dimerization and activation that uses this structural information and can explain the characteristic concave-up curvilinear Scatchard plots seen when EGF binding to intact EGFR is studied in living cells. We show that these curvilinear plots cannot be accounted for by simply ascribing different affinities to the autoinhibited and extended (dimeric) configurations of the receptor seen in structural studies. Concave-up plots can only be obtained by including in the mathematical model an additional binding event in which occupied EGFR dimers bind to an "external site." The external site may represent receptor interactions with coated-pit regions in the cell membrane or with other cellular components involved in receptor endocytosis and turnover. We conclude in this study and in the accompanying article that the active extended EGFR configuration binds EGF 5- to 20-fold more strongly than the autoinhibited monomeric receptor configuration. However, these extended receptors do not correspond directly with the "high-affinity" EGF-binding sites seen in EGF-binding studies on intact cells.
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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.