ArticleEMBO reports2001
Regulation of epidermal growth factor receptor endocytosis by wortmannin through activation of Rab5 rather than inhibition of phosphatidylinositol 3-kinase.
Article in EMBO reports, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- Insight into the role of clathrin-mediated endocytosis inhibitors in SARS-CoV-2 infection.Reviews in medical virology · 2023Review
- Article
- Role of Endocytosis Proteins in Gefitinib-Mediated EGFR Internalisation in Glioma Cells.Cells · 2021Article
- Gefitinib induces EGFR and α5β1 integrin co-endocytosis in glioblastoma cells.Cellular and molecular life sciences : CMLS · 2021Article
- An iron-dependent metabolic vulnerability underlies VPS34-dependence in RKO cancer cells.PloS one · 2020Article
- Adaptor protein-3 complex is required for Vangl2 trafficking and planar cell polarity of the inner ear.Molecular biology of the cell · 2019Article
- Vps34 regulates Rab7 and late endocytic trafficking through recruitment of the GTPase-activating protein Armus.Journal of cell science · 2016Article
- Active vacuolar H+ ATPase and functional cycle of Rab5 are required for the vacuolation defect triggered by PtdIns(3,5)P2 loss under PIKfyve or Vps34 deficiency.American journal of physiology. Cell physiology · 2016Article
- Nexus of signaling and endocytosis in oncogenesis driven by non-small cell lung cancer-associated epidermal growth factor receptor mutants.World journal of clinical oncology · 2014Review
- Impairment of Atg5-dependent autophagic flux promotes paraquat- and MPP⁺-induced apoptosis but not rotenone or 6-hydroxydopamine toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2013Article
- ARA7(Q69L) expression in transgenic Arabidopsis cells induces the formation of enlarged multivesicular bodies.Journal of experimental botany · 2013Article
- Phosphatidylinositol 3-kinase and Rab5 GTPase inversely regulate the Smad anchor for receptor activation (SARA) protein independently of transforming growth factor-β1.The Journal of biological chemistry · 2012Article
- Inhibition of endocytic processes by photodynamic therapy.Lasers in surgery and medicine · 2011Article
- Vascular endothelial growth factor acts through novel, pregnancy-enhanced receptor signalling pathways to stimulate endothelial nitric oxide synthase activity in uterine artery endothelial cells.The Biochemical journal · 2009Article
- Multipathway model enables prediction of kinase inhibitor cross-talk effects on migration of Her2-overexpressing mammary epithelial cells.Molecular pharmacology · 2008Article
- Phosphoinositide 3-kinase regulates the role of retromer in transcytosis of the polymeric immunoglobulin receptor.Experimental cell research · 2007Article
- Article
- Compartmental signal modulation: Endosomal phosphatidylinositol 3-phosphate controls endosome morphology and selective cargo sorting.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- Cardiac steroids induce changes in recycling of the plasma membrane in human NT2 cells.Molecular biology of the cell · 2004Article
- Modulation of Rab5 and Rab7 recruitment to phagosomes by phosphatidylinositol 3-kinase.Molecular and cellular biology · 2003Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The involvement of phosphatidylinositol 3-kinase (PI3K) in membrane trafficking in mammalian cells has largely come from experiments with wortmannin. This compound inhibits endosome fusion in vitro, possibly by inhibiting the production of phosphatidylinositol (PtdIns)-3-P, which co-regulates EEA1 with Rab5. However, the results from wortmannin inhibition experiments performed in vivo differ significantly. We have recently shown that wortmannin enlarges endosomes containing the epidermal growth factor receptor (EGFR) and enhances the lysosomal degradation of EGFR. In this report, we demonstrate that addition of the PI3K reaction products does not suppress wortmannin-induced enlargement of EGFR-containing endosomes and enhancement of EGFR degradation. Moreover, the effects of wortmannin on the intracellular trafficking of EGFR mimic those of the permanently activated Rab5 mutant, Rab5 Q79L, which stimulates endosome fusion. We also found that an inactive Rab5 mutant, Rab5 S34N, blocks wortmannin-induced endosome enlargement and that wortmannin stimulates the activation of Rab5. We further showed that wortmannin reduced the membrane association of p120 Ras GTPase-activating protein (GAP) and inhibited the interaction between Rab5 and p120 Ras GAP. We conclude that wortmannin alters intracellular trafficking of EGFR by activating Rab5 rather than by inhibiting PI3K.
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