ArticleBiochemistry2012
Temporal resolution of autophosphorylation for normal and oncogenic forms of EGFR and differential effects of gefitinib.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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
27 citing papers in PubMed, 43 citations in OpenAlex.
- Integrated isothermal shift assay and multi-omics identify melittin as a novel EGFR-targeting peptide to suppress NSCLC.Journal of translational medicine · 2026Article
- Isolation and characterization of extracellular vesicles from EGFR mutated lung cancer cells.Clinical and experimental medicine · 2025Article
- Spatial and signaling overlap of growth factor receptor systems at clathrin-coated sites.Molecular biology of the cell · 2024Article
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- Crosstalk of growth factor receptors at plasma membrane clathrin-coated sites.bioRxiv : the preprint server for biology · 2024Article
- Extracellular Vesicles and Epidermal Growth Factor Receptor Activation: Interplay of Drivers in Cancer Progression.Cancers · 2023Review
- Probing altered enzyme activity in the biochemical characterization of cancer.Bioscience reports · 2022Review
- Article
- Is Structure-Based Drug Design Ready for Selectivity Optimization?Journal of chemical information and modeling · 2020Article
- Cooperation and Interplay between EGFR Signalling and Extracellular Vesicle Biogenesis in Cancer.Cells · 2020Review
- Multisite EGFR phosphorylation is regulated by adaptor protein abundances and dimer lifetimes.Molecular biology of the cell · 2020Article
- Counting growth factors in single cells with infrared quantum dots to measure discrete stimulation distributions.Nature communications · 2019Article
- Modeling cell line-specific recruitment of signaling proteins to the insulin-like growth factor 1 receptor.PLoS computational biology · 2019Article
- Involvement of GLUT1-mediated glucose transport and metabolism in gefitinib resistance of non-small-cell lung cancer cells.Oncotarget · 2018Article
- Deep mutational analysis reveals functional trade-offs in the sequences of EGFR autophosphorylation sites.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Platination of cysteine by an epidermal growth factor receptor kinase-targeted hybrid agent.Chemical communications (Cambridge, England) · 2018Article
- Epidermal growth factor receptors containing a single tyrosine in their C-terminal tail bind different effector molecules and are signaling-competent.The Journal of biological chemistry · 2017Article
- 11β-HSD1 inhibition ameliorates diabetes-induced cardiomyocyte hypertrophy and cardiac fibrosis through modulation of EGFR activity.Oncotarget · 2017Article
- EGFR oligomerization organizes kinase-active dimers into competent signalling platforms.Nature communications · 2016Article
- Analysis of the Role of the C-Terminal Tail in the Regulation of the Epidermal Growth Factor Receptor.Molecular and cellular biology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases (RTK). EGFR overexpression or mutation in many different forms of cancers has highlighted its role as an important therapeutic target. Gefitinib, the first small molecule inhibitor of EGFR kinase function to be approved for the treatment of nonsmall cell lung cancer (NSCLC) by the FDA, demonstrates clinical activity primarily in patients with tumors that harbor somatic kinase domain mutations in EGFR. Here, we compare wild-type EGFR autophosphorylation kinetics to the L834R (also called L858R) EGFR form, one of the most common mutations in lung cancer patients. Using rapid chemical quench, time-resolved electrospray mass spectrometry (ESI-MS), and Western blot analyses, we examined the order of autophosphorylation in wild-type (WT) and L834R EGFR and the effect of gefitinib (Iressa) on the phosphorylation of individual tyrosines. These studies establish that there is a temporal order of autophosphorylation of key tyrosines involved in downstream signaling for WT EGFR and a loss of order for the oncogenic L834R mutant. These studies also reveal unique signature patterns of drug sensitivity for inhibition of tyrosine autophosphorylation by gefitinib: distinct for WT and oncogenic L834R mutant forms of EGFR. Fluorescence studies show that for WT EGFR the binding affinity for gefitinib is weaker for the phosphorylated protein while for the oncogenic mutant, L834R EGFR, the binding affinity of gefitinib is substantially enhanced and likely contributes to the efficacy observed clinically. This mechanistic information is important in understanding the molecular details underpinning clinical observations as well as to aid in the design of more potent and selective EGFR inhibitors.
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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.