ArticleMolecular biology of the cell2005
Growth factor receptor binding protein 2-mediated recruitment of the RING domain of Cbl to the epidermal growth factor receptor is essential and sufficient to support receptor endocytosis.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 144 citations in OpenAlex.
- Targeting EGFR Endocytosis and Signaling for Cancer Drug Delivery and Cancer Treatment.Cancers · 2026Review
- Laminar organization of molecular complexes in a clathrin coat revealed by nanoscale protein colocalization.Structure (London, England : 1993) · 2025Article
- Crosstalk between KDEL receptor and EGF receptor mediates cell proliferation and migration via STAT3 signaling.Cell communication and signaling : CCS · 2024Article
- Cbl and Cbl-b independently regulate EGFR through distinct receptor interaction modes.Molecular biology of the cell · 2023Article
- Regulation of microRNA expression by the adaptor protein GRB2.Scientific reports · 2023Article
- Knockout of c-Cbl slows EGFR endocytic trafficking and enhances EGFR signaling despite incompletely blocking receptor ubiquitylation.Pharmacology research & perspectives · 2021Article
- Endocytosis of BRASSINOSTEROID INSENSITIVE1 Is Partly Driven by a Canonical Tyr-Based Motif.The Plant cell · 2020Article
- Localization dynamics of endogenous fluorescently labeled RAF1 in EGF-stimulated cells.Molecular biology of the cell · 2019Article
- Article
- The Aryl Hydrocarbon Receptor Governs Epithelial Cell Invasion during Oropharyngeal Candidiasis.mBio · 2017Article
- Endocytosis of Ubiquitylation-Deficient EGFR Mutants via Clathrin-Coated Pits is Mediated by Ubiquitylation.Traffic (Copenhagen, Denmark) · 2015Article
- Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3).The Journal of biological chemistry · 2015Article
- Quantitative analysis reveals how EGFR activation and downregulation are coupled in normal but not in cancer cells.Nature communications · 2015Article
- 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
- Live-cell fluorescence imaging reveals high stoichiometry of Grb2 binding to the EGF receptor sustained during endocytosis.Journal of cell science · 2014Article
- Epithelial wounds induce differential phosphorylation changes in response to purinergic and EGF receptor activation.The American journal of pathology · 2013Article
- A cost-benefit analysis of the physical mechanisms of membrane curvature.Nature cell biology · 2013Review
- When ubiquitination meets phosphorylation: a systems biology perspective of EGFR/MAPK signalling.Cell communication and signaling : CCS · 2013Review
- Endocytosis of receptor tyrosine kinases.Cold Spring Harbor perspectives in biology · 2013Review
- Grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin.PloS one · 2013Article
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
Knockdown of growth factor receptor binding protein 2 (Grb2) by RNA interference strongly inhibits clathrin-mediated endocytosis of the epidermal growth factor receptor (EGFR). To gain insights into the function of Grb2 in EGFR endocytosis, we have generated cell lines in which endogenous Grb2 was replaced by yellow fluorescent protein (YFP)-tagged Grb2 expressed at the physiological level. In these cells, Grb2-YFP fully reversed the inhibitory effect of Grb2 knockdown on EGFR endocytosis and, moreover, trafficked together with EGFR during endocytosis. Overexpression of Grb2-binding protein c-Cbl did not restore endocytosis in Grb2-depleted cells. However, EGFR endocytosis was rescued in Grb2-depleted cells by chimeric proteins consisting of the Src homology (SH) 2 domain of Grb2 fused to c-Cbl. The "knockdown and rescue" analysis revealed that the expression of Cbl-Grb2/SH2 fusions containing RING finger domain of Cbl restores normal ubiquitylation and internalization of the EGFR in the absence of Grb2, consistent with the important role of the RING domain in EGFR endocytosis. In contrast, the carboxy-terminal domain of Cbl, when attached to Grb2 SH2 domain, had 4 times smaller endocytosis-rescue effect compared with the RING-containing chimeras. Together, the data suggest that the interaction of Cbl carboxy terminus with CIN85 has a minor and a redundant role in EGFR internalization. We concluded that Grb2-mediated recruitment of the functional RING domain of Cbl to the EGFR is essential and sufficient to support receptor endocytosis.
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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.