ArticleMolecular and cellular biology2002
Endosomal signaling of epidermal growth factor receptor stimulates signal transduction pathways leading to cell survival.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed, 295 citations in OpenAlex.
- Targeting EGFR Endocytosis and Signaling for Cancer Drug Delivery and Cancer Treatment.Cancers · 2026Review
- Biology and therapeutic potential of extracellular vesicle targeting and uptake.Nature reviews. Molecular cell biology · 2026Review
- Distinct Oxidative Stress Adaptations Driven by the Overexpression of miR-526b, miR-655, and COX-2 in Breast Cancer.International journal of molecular sciences · 2025Article
- A novel miniaturized filamentous phagemid as a gene delivery vehicle to target mammalian cells.Molecular therapy. Nucleic acids · 2025Article
- Ezrin defines TSC complex activation at endosomal compartments through EGFR-AKT signaling.eLife · 2025Article
- Roles of epidermal growth factor receptor, claudin-1 and occludin in multi-step entry of hepatitis C virus into polarized hepatoma spheroids.PLoS pathogens · 2023Article
- ACKnowledging the role of the Activated-Cdc42 associated kinase (ACK) in regulating protein stability in cancer.Small GTPases · 2023Review
- PTPN23 ubiquitination by WDR4 suppresses EGFR and c-MET degradation to define a lung cancer therapeutic target.Cell death & disease · 2023Article
- EGF-Receptor-Dependent TLR7 Signaling in Macrophages Promotes Glomerular Injury in Crescentic Glomerulonephritis.Laboratory investigation; a journal of technical methods and pathology · 2023Article
- Deterministic early endosomal maturations emerge from a stochastic trigger-and-convert mechanism.Nature communications · 2023Article
- Sialylation of EGFR by ST6GAL1 induces receptor activation and modulates trafficking dynamics.bioRxiv : the preprint server for biology · 2023Article
- Sorting nexin 10 sustains PDGF receptor signaling in glioblastoma stem cells via endosomal protein sorting.JCI insight · 2023Article
- Endosomal trafficking protein TBC-2 modulates stress resistance and lifespan through DAF-16-dependent and independent mechanisms.Aging cell · 2023Article
- Endosomal trafficking protein TBC-2 is required for the longevity of long-lived mitochondrial mutants.Frontiers in aging · 2023Article
- Functional selectivity of Receptor Tyrosine Kinases regulates distinct cellular outputs.Frontiers in cell and developmental biology · 2023Review
- Spatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival.Nature communications · 2022Article
- Article
- Review
- WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms.Autophagy · 2021Article
- Altered endocytosis in cellular senescence.Ageing research reviews · 2021Review
62 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In spite of intensified efforts to understand cell signaling from endosomes, there is no direct evidence demonstrating that endosomal signaling is sufficient to activate signal transduction pathways and no evidence to demonstrate that endosomal signaling is able to produce a biological outcome. The lack of breakthrough is due in part to the lack of means to generate endosomal signals without plasma membrane signaling. In this paper, we report the establishment of a system to specifically activate epidermal growth factor (EGF) receptor (EGFR) when it endocytoses into endosomes. We treated cells with EGF in the presence of AG-1478, a specific EGFR tyrosine kinase inhibitor, and monensin, which blocks the recycling of EGFR. This treatment led to the internalization of nonactivated EGF-EGFR complexes into endosomes. The endosome-associated EGFR was then activated by removing AG-1478 and monensin. During this procedure we did not observe any surface EGFR phosphorylation. We also achieved specific activation of endosome-associated EGFR without using monensin. By using this system, we provided original evidence demonstrating that (i) the endosome can serve as a nucleation site for the formation of signaling complexes, (ii) endosomal EGFR signaling is sufficient to activate the major signaling pathways leading to cell proliferation and survival, and (iii) endosomal EGFR signaling is sufficient to suppress apoptosis induced by serum withdrawal.
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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.