ArticleProceedings of the National Academy of Sciences of the United States of America2012
A single ligand is sufficient to activate EGFR dimers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 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
77 citing papers in PubMed, 153 citations in OpenAlex.
- Targeting EGFR Endocytosis and Signaling for Cancer Drug Delivery and Cancer Treatment.Cancers · 2026Review
- Recurrent cancer-associated ERBB4 mutations are transforming and confer resistance to targeted therapies.Molecular oncology · 2026Article
- Article
- Active regulation of the epidermal growth factor receptor by the membrane bilayer.bioRxiv : the preprint server for biology · 2025Article
- Selective targeting of oncogenic hotspot mutations of the HER2 extracellular domain.Nature chemical biology · 2025Article
- Confinement energy landscape classification reveals membrane receptor nano-organization mechanisms.Biophysical journal · 2024Article
- Drug-resistant EGFR mutations promote lung cancer by stabilizing interfaces in ligand-free kinase-active EGFR oligomers.Nature communications · 2024Article
- Article
- Structural dynamics of the active HER4 and HER2/HER4 complexes is finely tuned by different growth factors and glycosylation.bioRxiv : the preprint server for biology · 2024Article
- The Agonistic Activity of the Human Epidermal Growth Factor is Reduced by the D46G Substitution.Protein and peptide letters · 2024Article
- A perspective of fluorescence microscopy for cellular structural biology with EGFR as witness.Journal of microscopy · 2023Article
- The EGFR phosphatase RPTPγ is a redox-regulated suppressor of promigratory signaling.The EMBO journal · 2023Article
- Schizophrenia Animal Modeling with Epidermal Growth Factor and Its Homologs: Their Connections to the Inflammatory Pathway and the Dopamine System.Biomolecules · 2023Review
- Structure and dynamics of the EGFR/HER2 heterodimer.Cell discovery · 2023Article
- Structural arrangement of the active back-to-back dimer in N-glycosylated ErbB receptors is regulated by heterodimerization.Molecular biology research communications · 2023Article
- An extracellular receptor tyrosine kinase motif orchestrating intracellular STAT activation.Nature communications · 2022Article
- Validated determination of NRG1 Ig-like domain structure by mass spectrometry coupled with computational modeling.Communications biology · 2022Article
- Critical roles for EGFR and EGFR-HER2 clusters in EGF binding of SW620 human carcinoma cells.Journal of the Royal Society, Interface · 2022Article
- Antitumor activity of a lectibody targeting cancer-associated high-mannose glycans.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Article
17 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
Crystal structures of human epidermal growth factor receptor (EGFR) with bound ligand revealed symmetric, doubly ligated receptor dimers thought to represent physiologically active states. Such complexes fail to rationalize negative cooperativity of epidermal growth factor (EGF) binding to EGFR and the behavior of the ligandless EGFR homolog ErbB2/HER2, however. We report cell-based assays that provide evidence for active, singly ligated dimers of human EGFR and its homolog, ErbB4/HER4. We also report crystal structures of the ErbB4/HER4 extracellular region complexed with its ligand Neuregulin-1β that resolve two types of ErbB dimer when compared to EGFR:Ligand complexes. One type resembles the recently reported asymmetric dimer of Drosophila EGFR with a single high-affinity ligand bound and provides a model for singly ligated human ErbB dimers. These results unify models of vertebrate and invertebrate EGFR/ErbB signaling, imply that the tethered conformation of unliganded ErbBs evolved to prevent crosstalk among ErbBs, and establish a molecular basis for both negative cooperativity of ligand binding to vertebrate ErbBs and the absence of active ErbB2/HER2 homodimers in normal conditions.
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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.