ArticleCell2017
EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics.
Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers.
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
237 citing papers in PubMed, 389 citations in OpenAlex.
- Ligand-activated EGFR/MAPK signaling but not PI3K, are key resistance mechanisms to EGFR-therapy in colorectal cancer.Nature communications · 2025Trial
- Proliferation and differentiation in intestinal organoids are balanced by ligand-modulated EGFR trafficking.Life science alliance · 2026Article
- Rhomboid protease RHBDL2 is a calcium-activated suppressor of EGFR signalling in keratinocytes.Cellular and molecular life sciences : CMLS · 2026Article
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
- Amphiregulin drives EGFR-dependent genome stability in colorectal cancer and represents a targetable vulnerability.Oncogene · 2026Article
- IgE Occupancy and Antigen Valency Cooperate to Control FcεRI Aggregation Geometry and Signaling Efficiency.International journal of molecular sciences · 2026Article
- Does the ERBB/EGF Signaling Network Serve as a Nexus for Oncogenic Signals in Uveal Melanoma?Biomolecules · 2026Review
- Comparative Real-Time Kinetics of Ligand-Receptor Interactions Using Immobilization-Based Sensing Readouts.Analytical chemistry · 2026Article
- Opportunities and challenges in the development of evolving EGFR inhibitors to overcome EGFR TKIs resistance.Acta pharmacologica Sinica · 2026Review
- CAF-derived PAI-1 serves as an EGFR ligand and fuels KRAS-mutant pancreatic cancer.Nature communications · 2026Article
- Differential ErbB receptor dimerization modulates the ability of EGF receptor ligands to regulate metabolic flux.The Journal of biological chemistry · 2026Article
- EGFR and Its Ligands in Idiopathic Pulmonary Fibrosis: Predicting Clinical Outcomes and Molecular Endotyping Through In-Depth Analysis.Journal of Korean medical science · 2026Article
- ErbB family receptor dimerization dynamics and dysregulation via long-term single-molecule imaging.Cell · 2026Article
- The Epidermal Growth Factor Receptor (EGFR) as a means of neuro-immune cross-conversation.Journal of neuroinflammation · 2026Review
- Preservation of Human Colonic Stem Cells Requires an ERK Dynamics Checkpoint Mediated by AKT.bioRxiv : the preprint server for biology · 2026Article
- Targeting cancer expressed EGFR with a humanized monoclonal antibody.Scientific reports · 2026Article
- The role of kinase domain dimerization in EGFR activation.Structure (London, England : 1993) · 2026Article
- Adaptation of plateau frog peptide: From antimicrobial to angiogenic and proliferative functions.Journal of advanced research · 2026Article
- Epiregulin enhances periodontal tissue regeneration by promoting bone marrow mesenchymal stem cell functions under inflammatory niches.World journal of stem cells · 2026Article
- Quantitative Stimulated Emission Depletion (STED) Microscopy with DNA-Fluorophore Labels.ACS nano · 2026Article
177 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
11 authors at 4 institutions in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) regulates many crucial cellular programs, with seven different activating ligands shaping cell signaling in distinct ways. Using crystallography and other approaches, we show how the EGFR ligands epiregulin (EREG) and epigen (EPGN) stabilize different dimeric conformations of the EGFR extracellular region. As a consequence, EREG or EPGN induce less stable EGFR dimers than EGF-making them partial agonists of EGFR dimerization. Unexpectedly, this weakened dimerization elicits more sustained EGFR signaling than seen with EGF, provoking responses in breast cancer cells associated with differentiation rather than proliferation. Our results reveal how responses to different EGFR ligands are defined by receptor dimerization strength and signaling dynamics. These findings have broad implications for understanding receptor tyrosine kinase (RTK) signaling specificity. Our results also suggest parallels between partial and/or biased agonism in RTKs and G-protein-coupled receptors, as well as new therapeutic opportunities for correcting RTK signaling output.
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.