ArticleOncogene2010
Activity and cellular localization of an oncogenic glioblastoma multiforme-associated EGF receptor mutant possessing a duplicated kinase domain.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non-Small Cell Lung Cancer.Cancer research and treatment · 2022Article
- A Novel Oncogenic Driver in a Lung Adenocarcinoma Patient Harboring anFrontiers in oncology · 2020Article
- Lung adenocarcinoma patient with anJournal of thoracic disease · 2018Article
- Activation of the EGF Receptor by Ligand Binding and Oncogenic Mutations: The "Rotation Model".Cells · 2017Review
- BRAF(V600E) Kinase Domain Duplication Identified in Therapy-Refractory Melanoma Patient-Derived Xenografts.Cell reports · 2016Article
- Recent developments in receptor tyrosine kinases targeted anticancer therapy.Veterinary world · 2016Review
- EGFR Kinase Domain Duplication (EGFR-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to Afatinib.Cancer discovery · 2015Article
- Ginsenoside Rh2 inhibits growth of glioblastoma multiforme through mTor.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Inhibition of FoxO1 nuclear exclusion prevents metastasis of glioblastoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- EGFR signaling-dependent inhibition of glioblastoma growth by ginsenoside Rh2.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- EGFR-mutated lung cancer: a paradigm of molecular oncology.Oncotarget · 2010Review
- Oncogenic mutant forms of EGFR: lessons in signal transduction and targets for cancer therapy.FEBS letters · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A mutation of the epidermal growth factor receptor (EGFR) that results in a tandem kinase domain duplication (TKD-EGFR) has been described in glioblastoma multiforme biopsies and cell lines. Although the TKD-EGFR confers tumorigenicity, little is known about the molecular underpinnings of receptor dysregulation. Therefore, we transfected B82L mouse fibroblast cells devoid of endogenous EGFR to determine the molecular mechanisms of receptor activation when expressed in cells as well as the contribution of each duplicated kinase domain to receptor phosphorylation. The TKD-EGFR displayed chronically elevated basal autophosphorylation at five known phosphotyrosine sites. The chronically phosphorylated TKD-EGFR was also resistant to competitive inhibition of ligand-binding compared with wild-type EGFR (WT-EGFR) and showed undetectable levels of basal dimerization, suggesting the TKD-EGFR escapes known mechanisms of receptor downregulation. Immunofluorescence analyses revealed a substantial portion of the TKD-EGFR resides in the cytosol in an activated state, although surface-localized subsets of the receptor retain ligand responsiveness. Kinase activity-deficient knockouts of the N-terminal or the C-terminal kinase domains generated TKD-EGFRs that recapitulate the autophosphorylation/localization patterns of a constitutively activated receptor versus a WT-like EGFR, respectively. Investigation of the molecular activity of the TKD-EGFR yields evidence for a unique mechanism of constitutive activity and dual kinase domain activation.
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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.