ArticleThe Journal of biological chemistry2009
Rab5 isoforms differentially regulate the trafficking and degradation of epidermal growth factor receptors.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 106 citations in OpenAlex.
- Plasma membrane mediated GLUT10 mitochondrial targeting regulates intracellular ascorbic acid homeostasis.iScience · 2026Article
- RAB5c orchestrates LC3-associated phagocytosis to promote microbicidal function of macrophages.Science advances · 2026Article
- Rab5 nucleotide binding promotes oxidative metabolism to fuel hepatocellular carcinoma cell proliferation.The Journal of biological chemistry · 2026Article
- Lipid turnover and GEF recruitment collectively determine Rab5 recruitment and activation during the first step of early endosome formation.Nature communications · 2026Article
- Article
- Hyperactivation of RAB5 disrupts the endosomal Rab cascade leading to endolysosomal dysregulation in Down syndrome: A necessary role for increased APP gene dose.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- RAB5c controls the assembly of non-canonical autophagy machinery to promote phagosome maturation and microbicidal function of macrophages.bioRxiv : the preprint server for biology · 2025Article
- Cross-family small GTPase ubiquitination by the intracellular pathogenMolecular biology of the cell · 2024Article
- Membrane trafficking alterations in breast cancer progression.Frontiers in cell and developmental biology · 2024Review
- Review
- Macrocephaly and developmental delay caused by missense variants in RAB5C.Human molecular genetics · 2023Article
- The microenvironment-a general hypothesis on the homeostatic function of extracellular vesicles.FASEB bioAdvances · 2022Article
- A dominant negative variant ofProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Role of Endocytosis Proteins in Gefitinib-Mediated EGFR Internalisation in Glioma Cells.Cells · 2021Article
- Article
- Who's in control? Principles of Rab GTPase activation in endolysosomal membrane trafficking and beyond.The Journal of cell biology · 2021Review
- Endocytosis in the context-dependent regulation of individual and collective cell properties.Nature reviews. Molecular cell biology · 2021Review
- Article
- Role of bacterial infections in extracellular vesicles release and impact on immune response.Biomedical journal · 2021Review
- Rab26 suppresses migration and invasion of breast cancer cells through mediating autophagic degradation of phosphorylated Src.Cell death & disease · 2021Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Ligand-mediated endocytosis is an intricate regulatory mechanism for epidermal growth factor receptor (EGFR) signal transduction. Coordinated trafficking of EGFR ensures its temporal and spatial communication with downstream signaling effectors. We focused our work on Rab5, a monomeric GTPase shown to participate in early stages of the endocytic pathway. Rab5 has three isoforms (A, B, and C) sharing more than 90% of sequence identity. We individually ablated endogenous isoforms in HeLa cells with short interfering RNAs and examined the loss-of-function phenotypes. We found that suppression of Rab5A or 5B hampered the degradation of EGFR, whereas Rab5C depletion had very little effect. The differential delay of EGFR degradation also corresponds with retarded progression of EGFR from early to late endosomes. We investigated the activators/effectors of Rab5A that can potentially separate its potency in EGFR degradation from other isoforms and found that Rin1, a Rab5 exchange factor, preferably associated with Rab5A. Moreover, Rab5A activation is sensitive to EGF stimulation, and suppression of Rin1 diminished this sensitivity. Based on our results together with previous work showing that Rin1 interacts with signal transducing adapter molecule to facilitate the degradation of EGFR (Kong, C., Su, X., Chen, P. I., and Stahl, P. D. (2007) J. Biol. Chem. 282, 15294-15301), we hypothesize that the selective association of Rab5A and Rin1 contributes to the dominance of Rab5A in EGFR trafficking, whereas the other isoforms may have major functions unrelated to the EGFR degradation pathway.
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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.