2017
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 ResearchMeSH KeywordsCrystallography, X-RayEpigenEpiregulinErbB ReceptorsFluorescence Resonance Energy TransferHumansKineticsLigandsModels, MolecularProtein MultimerizationConceptsReceptor 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 agonism
2014
Complex Relationship between Ligand Binding and Dimerization in the Epidermal Growth Factor Receptor
Bessman NJ, Bagchi A, Ferguson KM, Lemmon MA. Complex Relationship between Ligand Binding and Dimerization in the Epidermal Growth Factor Receptor. Cell Reports 2014, 9: 1306-1317. PMID: 25453753, PMCID: PMC4254573, DOI: 10.1016/j.celrep.2014.10.010.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorLigand bindingExtracellular regionGrowth factor receptorIntact epidermal growth factor receptorEGFR extracellular regionComplex allosteric regulationExtracellular epidermal growth factor receptorFactor receptorLigand-binding affinityAllosteric regulationReceptor dimerizationEGFR dimerizationAllosteric linkagePathological mutationsOncogenic mutationsNegative cooperativityMutationsDimerizationUnexpected relationshipBindingSpecific ligandsPivotal roleRecent advancesReceptorsPutting together structures of epidermal growth factor receptors
Bessman NJ, Freed DM, Lemmon MA. Putting together structures of epidermal growth factor receptors. Current Opinion In Structural Biology 2014, 29: 95-101. PMID: 25460273, PMCID: PMC4268130, DOI: 10.1016/j.sbi.2014.10.002.Peer-Reviewed Original ResearchMeSH KeywordsEpidermal Growth FactorErbB ReceptorsHumansLigandsMicroscopy, ElectronProtein MultimerizationConceptsEpidermal growth factor receptorGrowth factor receptorIntact epidermal growth factor receptorChemical biology methodsNumerous crystal structuresFactor receptorTyrosine kinase domainVariety of inhibitorsKinase domainExtracellular regionMembrane environmentIntracellular regionBiology methodsIntact receptorReceptorsCancer therapyNext challengeCrystal structureMembraneActivationRegionInhibitorsDomain