2021
Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases
Sheetz J, Mathea S, Karvonen H, Malhotra K, Chatterjee D, Niininen W, Perttila R, Preuss F, Suresh K, Stayrook S, Tsutsui Y, Radhakrishnan R, Ungureanu D, Knapp S, Lemmon M. Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases. The FASEB Journal 2021, 35 DOI: 10.1096/fasebj.2021.35.s1.02446.Peer-Reviewed Original ResearchReceptor tyrosine kinasesPseudokinase domainTyrosine kinaseTyrosine kinase-mediated signalingKey cellular processesKinase-mediated signalingExtracellular cuesViable drug targetTransduce signalsCellular processesEmbryonic developmentPseudokinasesTissue homeostasisFuture dissectionReceptor dimerizationStructural insightsKinase activityCancer hallmarksSignaling mechanismDrug targetsPutative routesKinaseOncogenic driversSmall moleculesPhosphotransfer
2017
Dimerization 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
2015
Ligand regulation of a constitutively dimeric EGF receptor
Freed DM, Alvarado D, Lemmon MA. Ligand regulation of a constitutively dimeric EGF receptor. Nature Communications 2015, 6: 7380. PMID: 26060020, PMCID: PMC4465127, DOI: 10.1038/ncomms8380.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorLin-3Ligand-induced receptor dimerizationInsulin receptor family membersReceptor family membersLET-23Minor structural rearrangementsDomain compositionLigand regulationGrowth factor receptorDimerization armAllosteric changesExtracellular regionOligomerization stateReceptor dimerizationMutational analysisEGF receptorFactor receptorStructural rearrangementsKey eventsCovalent dimersStructural studiesFamily membersCaenorhabditisDimers
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 advancesReceptors
2009
Regulation of the epidermal growth factor receptor intracellular domain
Choi S, Lemmon M. Regulation of the epidermal growth factor receptor intracellular domain. The FASEB Journal 2009, 23: 883.2-883.2. DOI: 10.1096/fasebj.23.1_supplement.883.2.Peer-Reviewed Original ResearchC-terminal tailTyrosine kinase domainIntracellular domainJuxtamembrane regionJM regionEGFR intracellular domainEpidermal growth factor receptorC-tailEGFR extracellular regionC-tail regionReceptor intracellular domainEffects of mutationsReceptor tyrosine kinasesReceptor-receptor interactionsSmall-angle X-ray scatteringKinase assaysKinase domainGrowth factor receptorExtracellular regionReceptor dimerizationEGFR activationBaculovirus systemIntracellular dimerTyrosine kinaseDeletion mutations
2008
Ligand-induced ErbB receptor dimerization
Lemmon MA. Ligand-induced ErbB receptor dimerization. Experimental Cell Research 2008, 315: 638-648. PMID: 19038249, PMCID: PMC2667204, DOI: 10.1016/j.yexcr.2008.10.024.Peer-Reviewed Original ResearchConceptsReceptor dimerizationEGF receptorCell surfaceStructural studiesReceptor tyrosine kinasesReceptor extracellular regionExtracellular regionSimple overexpressionImportant new insightsTyrosine kinaseIntact receptorCell transformationStructural predictionsWhole receptorErbB familyErbB receptorsEGF bindingNegative cooperativityMechanistic componentsKey mechanistic componentNew insightsDimerizationReceptorsHomodimerizationKinase
1997
Kit Receptor Dimerization Is Driven by Bivalent Binding of Stem Cell Factor*
Lemmon M, Pinchasi D, Zhou M, Lax I, Schlessinger J. Kit Receptor Dimerization Is Driven by Bivalent Binding of Stem Cell Factor*. Journal Of Biological Chemistry 1997, 272: 6311-6317. PMID: 9045650, DOI: 10.1074/jbc.272.10.6311.Peer-Reviewed Original ResearchConceptsStem cell factorKIT dimerizationReceptor dimerizationExtracellular domainCell factorFourth Ig-like domainColony-stimulating factor-1Receptor tyrosine kinasesIg-like domainsCytokine stem cell factorDomain bindsPlatelet-derived growth factorGrowth factorLike domainDimer bindsMost growth factorsTyrosine kinaseDimerization siteConformational changesReceptor KITAnalytical ultracentrifugationForms of KITBivalent bindingFactor 1DimerizationTwo EGF molecules contribute additively to stabilization of the EGFR dimer
Lemmon M, Bu Z, Ladbury J, Zhou M, Pinchasi D, Lax I, Engelman D, Schlessinger J. Two EGF molecules contribute additively to stabilization of the EGFR dimer. The EMBO Journal 1997, 16: 281-294. PMID: 9029149, PMCID: PMC1169635, DOI: 10.1093/emboj/16.2.281.Peer-Reviewed Original ResearchConceptsEpidermal growth factorReceptor dimerizationEGF moleculesPrecise molecular detailsHuman growth hormone receptorReceptor-receptor interactionsGrowth factorInterferon-gamma receptorEGFR dimersSignaling eventsMolecular detailsReceptor oligomerizationGrowth hormone receptorExtracellular domainEGFR familyCell surfaceMonomer bindsSubsequent associationDimerizationHormone receptorsTitration calorimetrySmall-angle X-ray scatteringBindingReceptorsMultivalent binding