ArticleProceedings of the National Academy of Sciences of the United States of America2004
The tethered configuration of the EGF receptor extracellular domain exerts only a limited control of receptor function.
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. Cited by 49 papers.
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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
49 citing papers in PubMed, 104 citations in OpenAlex.
- A potential mechanism for tetraspanin CD82-mediated regulation of EGFR.Life science alliance · 2026Article
- Drug-resistant EGFR mutations promote lung cancer by stabilizing interfaces in ligand-free kinase-active EGFR oligomers.Nature communications · 2024Article
- Structure and dynamics of the EGFR/HER2 heterodimer.Cell discovery · 2023Article
- Review
- Molecular Targeting of Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR).Molecules (Basel, Switzerland) · 2021Review
- Mechanisms of Action of EGFR Tyrosine Kinase Receptor Incorporated in Extracellular Vesicles.Cells · 2020Review
- Oncogenic mutations at the EGFR ectodomain structurally converge to remove a steric hindrance on a kinase-coupled cryptic epitope.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Review
- Piecing it together: Unraveling the elusive structure-function relationship in single-pass membrane receptors.Biochimica et biophysica acta. Biomembranes · 2017Review
- Rigidity of the extracellular part of HER2: Evidence from engineering subdomain interfaces and shared-helix DARPin-DARPin fusions.Protein science : a publication of the Protein Society · 2017Article
- HTS-compatible FRET-based conformational sensors clarify membrane receptor activation.Nature chemical biology · 2017Article
- Selective Targeting of the L858R Mutation (EGFR) in Non-Small Cell Lung Cancer: A Mechanism for Advancing Targeted Chemotherapy.Frontiers in oncology · 2017Article
- Enhanced dimerization drives ligand-independent activity of mutant epidermal growth factor receptor in lung cancer.Molecular biology of the cell · 2015Article
- Putting together structures of epidermal growth factor receptors.Current opinion in structural biology · 2014Review
- Complex relationship between ligand binding and dimerization in the epidermal growth factor receptor.Cell reports · 2014Article
- Membrane interaction of bound ligands contributes to the negative binding cooperativity of the EGF receptor.PLoS computational biology · 2014Article
- A Meta-Analysis on the Relations between EGFR R521K Polymorphism and Risk of Cancer.International journal of genomics · 2014Article
- Article
- Hyperactivation of constitutively dimerized oncogenic EGF receptors by autocrine loops.Oncogene · 2013Article
- Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Quantitative epidermal growth factor (EGF)-binding experiments have shown that the EGF-receptor (EGFR) is displayed on the surface of intact cells in two forms, a minority of high-affinity and a majority of low-affinity EGFRs. On the basis of the three-dimensional structure of the extracellular ligand binding domain of the EGFR, it was proposed that the intramolecularly tethered and autoinhibited configuration corresponds to the low-affinity receptor, whereas the extended configuration accounts for the high-affinity EGFRs on intact cells. Here we test this model by analyzing the properties of EGFRs mutated in the specific regions responsible for receptor autoinhibition and dimerization, respectively. Our results show that mutagenic disruption of the autoinhibitory tether in EGFR results in a decrease in the dissociation rate of EGF without a detectable change in EGFR activation and signaling through EGFR even in response to stimulation with low concentrations of EGF. Mutagenic disruption of the dimerization arm, on the other hand, increased the rate of EGF dissociation and impaired EGFR activation and signaling via the EGFR. This study demonstrates that the extended configuration of EGFR does not account for the apparent high-affinity EGF-binding to EGFR on intact cells. Furthermore, the autoinhibition conferred by the tethered configuration of the extracellular ligand-binding domain provides only a limited control of EGFR function.
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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.