The epidermal growth factor receptor (EGFR) is activated by dimerization, but activation also generates higher-order multimers, whose nature and function are poorly understood. We have characterized ligand-induced dimerization and multimerization of EGFR using single-molecule analysis, and show that multimerization can be blocked by mutations in a specific region of Domain IV of the extracellular module. These mutations reduce autophosphorylation of the C-terminal tail of EGFR and attenuate phosphorylation of phosphatidyl inositol 3-kinase, which is recruited by EGFR. The catalytic activity of EGFR is switched on through allosteric activation of one kinase domain by another, and we show that if this is restricted to dimers, then sites in the tail that are proximal to the kinase domain are phosphorylated in only one subunit. We propose a structural model for EGFR multimerization through self-association of ligand-bound dimers, in which the majority of kinase domains are activated cooperatively, thereby boosting tail phosphorylation.
Self-phosphorylation of epidermal growth factor receptor: evidence for a model of intermolecular allosteric activation
Epidermal growth factor induces rapid, reversible aggregation of the purified epidermal growth factor receptor
Optimized codon usage and chromophore mutations provide enhanced sensitivity with the green fluorescent protein
Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers.
Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2
Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor.
Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha
Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains
Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib
Ligand-induced dimer-tetramer transition during the activation of the cell surface epidermal growth factor receptor-A multidimensional microscopy analysis
Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface
Spatial structure of the transmembrane domain heterodimer of ErbB1 and ErbB2 receptor tyrosine kinases
Distribution of resting and ligand-bound ErbB1 and ErbB2 receptor tyrosine kinases in living cells using number and brightness analysis
Structural evidence for loose linkage between ligand binding and kinase activation in the epidermal growth factor receptor
Structural analysis of the mechanism of inhibition and allosteric activation of the kinase domain of HER2 protein.
Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex
Collagen induces activation of DDR1 through lateral dimer association and phosphorylation between dimers
Coupled regulation by the juxtamembrane and sterile α motif (SAM) linker is a hallmark of ephrin tyrosine kinase evolution
Epidermal growth factor receptors containing a single tyrosine in their C-terminal tail bind different effector molecules and are signaling-competent
Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling
Allosteric regulation of epidermal growth factor (EGF) receptor ligand binding by tyrosine kinase inhibitors
Charge and Polarity Preferences forN -Glycosylation: A Genome-WideIn Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells
Altered conformational landscape and dimerization dependency underpins the activation of EGFR by α C-β 4 loop insertion mutations
Structure and Dynamics of the EGF Receptor as Revealed by Experiments and Simulations and Its Relevance to Non-Small Cell Lung Cancer
Inhibitor-induced HER2-HER3 heterodimerisation promotes proliferation through a novel dimer interface.
EGF Receptor Stalls upon Activation as Evidenced by Complementary Fluorescence Correlation Spectroscopy and Fluorescence Recovery after Photobleaching Measurements
Processing Temporal Growth Factor Patterns by an Epidermal Growth Factor Receptor Network Dynamically Established in Space.
Conserved roles for receptor tyrosine kinase extracellular regions in regulating receptor and pathway activity.
Basic Amino Acids Within the Juxtamembrane Domain of the Epidermal Growth Factor Receptor Regulate Receptor Dimerization and Auto-phosphorylation.
CD99-PTPN12 Axis Suppresses Actin Cytoskeleton-Mediated Dimerization of Epidermal Growth Factor Receptor
Molecular Targeting of Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR).
Structure-function analysis of oncogenic EGFR Kinase Domain Duplication reveals insights into activation and a potential approach for therapeutic targeting.
Binding of single-mutant epidermal growth factor (EGF) ligands alters the stability of the EGF receptor dimer and promotes growth signaling.
Resolving Membrane Protein-Protein Interactions in Live Cells with Pulsed Interleaved Excitation Fluorescence Cross-Correlation Spectroscopy.
This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.