ArticleScience signaling2014
Structural analysis of the EGFR/HER3 heterodimer reveals the molecular basis for activating HER3 mutations.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 68 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Molecular and Clinicopathological Biomarkers Predicting Brain Metastasis in Triple-Negative Breast Cancer: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Identification of a novel HER3 activating mutation homologous to EGFR-L858R in lung cancer.Oncotarget · 2016Trial
- Modulating pseudokinase conformation from the ATP-binding site.Structure (London, England : 1993) · 2026Article
- The multifaceted roles of receptor tyrosine pseudokinases in cellular signalling.Biochemical Society transactions · 2026Review
- ErbB family receptor dimerization dynamics and dysregulation via long-term single-molecule imaging.Cell · 2026Article
- The role of kinase domain dimerization in EGFR activation.Structure (London, England : 1993) · 2026Article
- Loss of ErbB3 redirects Integrin β1 from early endosomal recycling to secretion in extracellular vesicles.The Journal of cell biology · 2026Article
- Structural analysis of HER2-trastuzumab complex reveals receptor conformational adaptation.Science advances · 2025Article
- Identification of EcpK, a bacterial tyrosine pseudokinase important for exopolysaccharide biosynthesis inJournal of bacteriology · 2025Article
- Scaffolding Activities of Pseudodeacetylase HDAC7.ACS chemical biology · 2025Review
- MDTAP: a tool to analyze permeation events across membrane proteins.Bioinformatics advances · 2025Article
- Biparatopic HER2-targeted nanobody binder synergizes with trastuzumab in resistant tumor cells.Frontiers in immunology · 2025Article
- ERBB2/ ERBB3-mutated S100/ SOX10-positive unclassified high-grade uterine sarcoma: first detailed description of a novel entity.Virchows Archiv : an international journal of pathology · 2024Article
- Trans-activating mutations of the pseudokinase ERBB3.Oncogene · 2024Article
- HER4 and EGFR Activate Cell Signaling in NRG1 Fusion-Driven Cancers: Implications for HER2-HER3-specific Versus Pan-HER Targeting Strategies.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2024Article
- Identification of Potent Inhibitors Targeting EGFR and HER3 for Effective Treatment of Chemoresistance in Non-Small Cell Lung Cancer.Molecules (Basel, Switzerland) · 2023Article
- Emerging functions of pseudoenzymes.The Biochemical journal · 2023Review
- Wingless/It/β-catenin signaling in liver metastasis from colorectal cancer: A focus on biological mechanisms and therapeutic opportunities.World journal of gastroenterology · 2023Review
- Advancing Targeted Protein Degradation via Multiomics Profiling and Artificial Intelligence.Journal of the American Chemical Society · 2023Review
- Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
- Correction · 2015-09-01Error in Data · Error in Image · Falsification/Fabrication of Data · Investigation by Company/Institution · Investigation by ORI · Manipulation of Images · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · · Findings of research misconduct (P Littlefield): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570207/; P Littlefield named for fabrication/errors;
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The human epidermal growth factor receptor (HER) tyrosine kinases homo- and heterodimerize to activate downstream signaling pathways. HER3 is a catalytically impaired member of the HER family that contributes to the development of several human malignancies and is mutated in a subset of cancers. HER3 signaling depends on heterodimerization with a catalytically active partner, in particular epidermal growth factor receptor (EGFR) (the founding family member, also known as HER1) or HER2. The activity of homodimeric complexes of catalytically active HER family members depends on allosteric activation between the two kinase domains. To determine the structural basis for HER3 signaling through heterodimerization with a catalytically active HER family member, we solved the crystal structure of the heterodimeric complex formed by the isolated kinase domains of EGFR and HER3. The structure showed HER3 as an allosteric activator of EGFR and revealed a conserved role of the allosteric mechanism in activation of HER family members through heterodimerization. To understand the effects of cancer-associated HER3 mutations at the molecular level, we solved the structures of two kinase domains of HER3 mutants, each in a heterodimeric complex with the kinase domain of EGFR. These structures, combined with biochemical analysis and molecular dynamics simulations, indicated that the cancer-associated HER3 mutations enhanced the allosteric activator function of HER3 by redesigning local interactions at the dimerization interface.
Indexed as
Identifiers
What OpenQuestion holds
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.