ArticleProceedings of the National Academy of Sciences of the United States of America2012
Suppression of EGFR endocytosis by dynamin depletion reveals that EGFR signaling occurs primarily at the plasma membrane.
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 91 papers.
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Who cites it
91 citing papers in PubMed, 160 citations in OpenAlex.
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- Dynamics of the formation of flat clathrin lattices in response to growth factor stimulus.PLoS computational biology · 2026Article
- Temporal photoproximity labeling of ligand-activated EGFR neighborhoods using MultiMap.Nature chemical biology · 2026Article
- Molecularly Built Ligands Degrade Membrane Receptors via Enhancing Their Accumulation in Lysosomes.ACS central science · 2025Article
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- The AP-2 complex interacts with γ-TuRC and regulates the proliferative capacity of neural progenitors.Life science alliance · 2024Article
- EGFR trafficking: effect of dimerization, dynamics, and mutation.Frontiers in oncology · 2023Review
- Regulation of EGF-stimulated activation of the PI-3K/AKT pathway by exocyst-mediated exocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- 1-Deoxysphingolipid synthesis compromises anchorage-independent growth and plasma membrane endocytosis in cancer cells.Journal of lipid research · 2022Article
- Review
- Critical roles for EGFR and EGFR-HER2 clusters in EGF binding of SW620 human carcinoma cells.Journal of the Royal Society, Interface · 2022Article
- Endocytosis at the Crossroad of Polarity and Signaling Regulation: Learning fromInternational journal of molecular sciences · 2022Review
- Fyn and TOM1L1 are recruited to clathrin-coated pits and regulate Akt signaling.The Journal of cell biology · 2022Article
- Spatial-proteomics reveals phospho-signaling dynamics at subcellular resolution.Nature communications · 2021Article
- Role of Endocytosis Proteins in Gefitinib-Mediated EGFR Internalisation in Glioma Cells.Cells · 2021Article
- EGFR-RAS-MAPK signaling is confined to the plasma membrane and associated endorecycling protrusions.The Journal of cell biology · 2021Article
- NDRG1 enhances the sensitivity of cetuximab by modulating EGFR trafficking in colorectal cancer.Oncogene · 2021Article
- Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The role of endocytosis in the control of EGF receptor (EGFR) activation and cell signaling was explored by using mouse fibroblasts in which dynamin was conditionally depleted. Dynamin is a GTPase shown to play an important role in the control clathrin mediated endocytosis of EGFR and other cell surface receptors. In this report, we demonstrate that EGF binding activity and the display of high and low affinity EGFRs on the cell surface are not affected by dynamin depletion. By contrast, dynamin depletion leads to a strong inhibition of EGFR endocytosis, robust enhancement of EGFR autophosphorylation and ubiquitination, and slower kinetics of EGFR degradation. Surprisingly, MAPK stimulation induced by either low or high EGF concentrations is not affected by dynamin depletion. While a similar initial Akt response is detected in control or dynamin depleted fibroblasts, a somewhat more sustained Akt stimulation is detected in the dynamin depleted cells. These experiments demonstrate that dynamin-mediated endocytosis leads to attenuation of EGFR activation and degradation and that stimulation of the MAPK response and Akt activation are primarily mediated by activated EGFR located in the plasma membrane.
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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.