ArticleACS chemical biology2012
Bipartite tetracysteine display reveals allosteric control of ligand-specific EGFR activation.
Article in ACS chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 65 citations in OpenAlex.
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
- Differential ErbB receptor dimerization modulates the ability of EGF receptor ligands to regulate metabolic flux.The Journal of biological chemistry · 2026Article
- Article
- The Yin and Yang of ERBB4: Tumor Suppressor and Oncoprotein.Pharmacological reviews · 2022Review
- Article
- Allosteric Inhibition of the Epidermal Growth Factor Receptor.Biochemistry · 2021Article
- The Biased Ligands NGF and NT-3 Differentially Stabilize Trk-A Dimers.Biophysical journal · 2021Article
- The biophysical basis of receptor tyrosine kinase ligand functional selectivity: Trk-B case study.The Biochemical journal · 2020Article
- Cooperation and Interplay between EGFR Signalling and Extracellular Vesicle Biogenesis in Cancer.Cells · 2020Review
- Discrete Coiled Coil Rotamers Form within the EGFRvIII Juxtamembrane Domain.Biochemistry · 2020Article
- Receptor tyrosine kinase activation: From the ligand perspective.Current opinion in cell biology · 2020Review
- More than the sum of the parts: Toward full-length receptor tyrosine kinase structures.IUBMB life · 2019Review
- The RTK Interactome: Overview and Perspective on RTK Heterointeractions.Chemical reviews · 2019Review
- Mechanism of Allosteric Coupling into and through the Plasma Membrane by EGFR.Cell chemical biology · 2018Article
- Article
- A sensitive assay reveals structural requirements for α-synuclein fibril growth.The Journal of biological chemistry · 2017Article
- A Conserved Ectodomain-Transmembrane Domain Linker Motif Tunes the Allosteric Regulation of Cell Surface Receptors.The Journal of biological chemistry · 2016Article
- Moderate and strong static magnetic fields directly affect EGFR kinase domain orientation to inhibit cancer cell proliferation.Oncotarget · 2016Article
- Rotamer-Restricted Fluorogenicity of the Bis-Arsenical ReAsH.Journal of the American Chemical Society · 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
4 authors at 1 institution in 1 country.
Funding
Abstract
Aberrant activation of the epidermal growth factor receptor (EGFR), a prototypic receptor tyrosine kinase, is critical to the biology of many common cancers. The molecular events that define how EGFR transmits an extracellular ligand binding event through the membrane are not understood. Here we use a chemical tool, bipartite tetracysteine display, to report on ligand-specific conformational changes that link ligand binding and kinase activation for full-length EGFR on the mammalian cell surface. We discover that EGF binding is communicated to the cytosol through formation of an antiparallel coiled coil within the intracellular juxtamembrane (JM) domain. This conformational transition is functionally coupled to receptor activation by EGF. In contrast, TGFα binding is communicated to the cytosol through formation of a discrete, alternative helical interface. These findings suggest that the JM region can differentially decode extracellular signals and transmit them to the cell interior. Our results provide new insight into how EGFR communicates ligand-specific information across the membrane.
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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.