ArticleMolecular biology of the cell2020
Multisite EGFR phosphorylation is regulated by adaptor protein abundances and dimer lifetimes.
Article in Molecular biology of the cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 39 citations in OpenAlex.
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
- Loss of LLGL1 Elevates EGFR/RAS/MAPK Signaling and Remodels EMT Markers in Huh-7 Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2026Article
- Platelet-Derived Components for Skin and Bone Aging and Age-Associated Pathologies: Mechanisms, Bioengineering Strategies, and Clinical Translation.Molecules (Basel, Switzerland) · 2026Review
- ALCAM-CD6 axis suppression: a key determinant of immune-mediated metastasis recurrence in stage III non-small cell lung cancer.Journal for immunotherapy of cancer · 2025Article
- EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Spatial and signaling overlap of growth factor receptor systems at clathrin-coated sites.Molecular biology of the cell · 2024Article
- The CD6 interactome orchestrates ligand-independent T cell inhibitory signaling.Cell communication and signaling : CCS · 2024Article
- Crosstalk of growth factor receptors at plasma membrane clathrin-coated sites.bioRxiv : the preprint server for biology · 2024Article
- Progress in Glioma Stem Cell Research.Cancers · 2023Review
- Quantification of ligand and mutation-induced bias in EGFR phosphorylation in direct response to ligand binding.Nature communications · 2023Article
- Article
- The EGFR phosphatase RPTPγ is a redox-regulated suppressor of promigratory signaling.The EMBO journal · 2023Article
- Targeted Quantification of Protein Phosphorylation and Its Contributions towards Mathematical Modeling of Signaling Pathways.Molecules (Basel, Switzerland) · 2023Review
- An Optimized Single-Molecule Pull-Down Assay for Quantification of Protein Phosphorylation.Journal of visualized experiments : JoVE · 2022Article
- Data-driven learning how oncogenic gene expression locally alters heterocellular networks.Nature communications · 2022Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Differential epidermal growth factor receptor (EGFR) phosphorylation is thought to couple receptor activation to distinct signaling pathways. However, the molecular mechanisms responsible for biased signaling are unresolved due to a lack of insight into the phosphorylation patterns of full-length EGFR. We extended a single-molecule pull-down technique previously used to study protein-protein interactions to allow for robust measurement of receptor phosphorylation. We found that EGFR is predominantly phosphorylated at multiple sites, yet phosphorylation at specific tyrosines is variable and only a subset of receptors share phosphorylation at the same site, even with saturating ligand concentrations. We found distinct populations of receptors as soon as 1 min after ligand stimulation, indicating early diversification of function. To understand this heterogeneity, we developed a mathematical model. The model predicted that variations in phosphorylation are dependent on the abundances of signaling partners, while phosphorylation levels are dependent on dimer lifetimes. The predictions were confirmed in studies of cell lines with different expression levels of signaling partners, and in experiments comparing low- and high-affinity ligands and oncogenic EGFR mutants. These results reveal how ligand-regulated receptor dimerization dynamics and adaptor protein concentrations play critical roles in EGFR signaling.
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.