EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics
Freed DM, Bessman NJ, Kiyatkin A, Salazar-Cavazos E, Byrne PO, Moore JO, Valley CC, Ferguson KM, Leahy DJ, Lidke DS, Lemmon MA. EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics. Cell 2017, 171: 683-695.e18. PMID: 28988771, PMCID: PMC5650921, DOI: 10.1016/j.cell.2017.09.017.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesEpidermal growth factor receptorEGFR ligandsEGFR extracellular regionG protein-coupled receptorsDifferent EGFR ligandsCellular programsDifferent activating ligandsEGFR dimersCell signalingGrowth factor receptorExtracellular regionDimeric conformationEGFR dimerizationNew therapeutic opportunitiesReceptor dimersTyrosine kinaseBreast cancer cellsDimerization strengthActivating ligandsFactor receptorCancer cellsEpigenTherapeutic opportunitiesBiased agonismDimerization of Tie2 mediated by its membrane-proximal FNIII domains
Moore JO, Lemmon MA, Ferguson KM. Dimerization of Tie2 mediated by its membrane-proximal FNIII domains. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 4382-4387. PMID: 28396397, PMCID: PMC5410832, DOI: 10.1073/pnas.1617800114.Peer-Reviewed Original ResearchConceptsExtracellular regionFNIII domainsResolution X-ray crystal structureMembrane-proximal fibronectin type III domainsDomain-mediated interactionsDifferent cellular contextsLigand-binding regionHigher-order oligomersTie2 activationFibronectin type III domainReceptor tyrosine kinasesTyrosine kinase familyEGF-homology domainThird FNIII domainType III domainPrevious structural studiesStructural studiesHomology domainCellular contextKinase familyDimer interfaceDimerization modeReceptor dimerizationTyrosine kinasePrimary activator