2018
Regulation of Kinase Activity in the Caenorhabditis elegans EGF Receptor, LET-23
Liu L, Thaker TM, Freed DM, Frazier N, Malhotra K, Lemmon MA, Jura N. Regulation of Kinase Activity in the Caenorhabditis elegans EGF Receptor, LET-23. Structure 2018, 26: 270-281.e4. PMID: 29358026, PMCID: PMC5803352, DOI: 10.1016/j.str.2017.12.012.Peer-Reviewed Original ResearchConceptsLET-23Allosteric activatorEGF receptorAllosteric activation mechanismFull-length receptorCaenorhabditis elegansActive kinaseKinase domainAllosteric activationKinase activityReceptor dimersEGFR kinaseKinaseHuman EGFRDistinct rolesHuman counterpartActivation mechanismActivatorReceptorsElegansHeterodimerizationMutationsCrystal structureRegulationEGFR
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
2010
Structural Basis for Negative Cooperativity in Growth Factor Binding to an EGF Receptor
Alvarado D, Klein DE, Lemmon MA. Structural Basis for Negative Cooperativity in Growth Factor Binding to an EGF Receptor. Cell 2010, 142: 568-579. PMID: 20723758, PMCID: PMC2925043, DOI: 10.1016/j.cell.2010.07.015.Peer-Reviewed Original ResearchConceptsEGFR extracellular regionEpidermal growth factor receptorExtracellular regionEGF receptorDifferent signaling propertiesLigand-binding eventsLigand-induced dimerizationIntracellular tyrosine kinase domainNegative cooperativityCooperative ligand bindingTyrosine kinase domainAllosteric regulationEGF-binding sitesKinase domainFactor bindingGrowth factor receptorGrowth factor bindingStructural basisLigand bindingEGFR ligandsSignaling propertiesFactor receptorReduced affinityAsymmetric dimerUnoccupied sites
2009
ErbB2/HER2/Neu resembles an autoinhibited invertebrate EGF receptor
Alvarado D, Klein D, Lemmon M. ErbB2/HER2/Neu resembles an autoinhibited invertebrate EGF receptor. The FASEB Journal 2009, 23: 884.3-884.3. DOI: 10.1096/fasebj.23.1_supplement.884.3.Peer-Reviewed Original ResearchReceptor tyrosine kinase ErbB2Human cancersAutoinhibitory interactionsExtracellular regionInterdomain interactionsEGF receptorErbB2 signalingOrphan receptorOncogenic propertiesHuman EGFRErbB receptorsImportant therapeutic targetErbB2Structural studiesTherapeutic targetNovel aspectsReceptorsAutoinhibitoryAutoinhibitionSignalingOverexpressionImportant implicationsRegulationTherapeutic approachesEGFR
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 insightsDimerizationReceptorsHomodimerizationKinaseHarnessing Novel Secreted Inhibitors of EGF Receptor Signaling for Breast Cancer Treatment
Lemmon M. Harnessing Novel Secreted Inhibitors of EGF Receptor Signaling for Breast Cancer Treatment. 2008 DOI: 10.21236/ada488172.Peer-Reviewed Original ResearchEGF receptor family membersEGF receptor signalingEGF-like ligandsReceptor family membersNew structural informationFruit flyYeast surface displayEGF receptorEGFR ligandsSecreted inhibitorsProtein scaffoldsReceptor signalingFunctional fragmentsSurface displayHuman EGFProtein therapeuticsTherapeutic designGrowth factorStructural informationNew therapeuticsExperimental approachStructure determinationFamily membersDrosophilaReceptorsMechanism of Activation and Inhibition of the HER4/ErbB4 Kinase
Qiu C, Tarrant MK, Choi SH, Sathyamurthy A, Bose R, Banjade S, Pal A, Bornmann WG, Lemmon MA, Cole PA, Leahy DJ. Mechanism of Activation and Inhibition of the HER4/ErbB4 Kinase. Structure 2008, 16: 460-467. PMID: 18334220, PMCID: PMC2858219, DOI: 10.1016/j.str.2007.12.016.Peer-Reviewed Original ResearchConceptsErbB4 kinaseEGF receptorBa/F3 cellsReceptor tyrosine kinasesMechanism of activationHER4/ErbB4ErbB family membersKinase domainHER2/ErbB2Kinase activationMutagenesis studiesTyrosine kinaseF3 cellsKinaseDimer conformationErbB familyNormal developmentInactive formAsymmetric dimerMammary glandErbB4ActivationFamily members
2007
Ligand-Induced Structural Transitions in ErbB Receptor Extracellular Domains
Dawson JP, Bu Z, Lemmon MA. Ligand-Induced Structural Transitions in ErbB Receptor Extracellular Domains. Structure 2007, 15: 942-954. PMID: 17697999, DOI: 10.1016/j.str.2007.06.013.Peer-Reviewed Original ResearchConceptsExtracellular regionDimerization siteLow-resolution molecular envelopeEpidermal growth factor receptor (EGFR) activationGrowth factor receptor activationAutoinhibitory intramolecular interactionMajor domain rearrangementsSmall-angle X-ray scatteringReceptor extracellular domainDomain rearrangementsEGF receptorExtracellular domainLigand bindingEGFR mutantsReceptor conformationMutantsMolecular envelopeExtended conformationNew insightsReceptor activationCrystallographic studiesConformationIntramolecular interactionsReceptorsX-ray scatteringHarnessing Novel Secreted Inhibitors of EGF Receptor Signaling for Breast Cancer Treatment
Lemmon M. Harnessing Novel Secreted Inhibitors of EGF Receptor Signaling for Breast Cancer Treatment. 2007 DOI: 10.21236/ada471085.Peer-Reviewed Original ResearchEGF receptor family membersEGF receptor signalingEGF-like ligandsReceptor family membersNew structural informationFruit flyYeast surface displayEGF receptorSecreted inhibitorsEGFR ligandsProtein scaffoldsReceptor signalingFunctional fragmentsSurface displayHuman EGFProtein therapeuticsTherapeutic designGrowth factorNew therapeuticsStructural informationExperimental approachStructure determinationFamily membersDrosophilaReceptorsActivation and Inhibition of the EGF Receptor
Lemmon M. Activation and Inhibition of the EGF Receptor. The FASEB Journal 2007, 21: a46-a46. DOI: 10.1096/fasebj.21.5.a46-b.Peer-Reviewed Original ResearchReceptor tyrosine kinasesEGFR extracellular regionEGF-induced dimerizationActivation of EGFRErbB family receptor tyrosine kinasesKekkon-1D. melanogasterEpidermal growth factor receptorC. elegansLigand sinkMembrane proteinsGrowth factor receptorExtracellular regionEGF receptorExtracellular domainTyrosine kinaseCurrent mechanistic viewsCell surfaceHuman cancersCell growthOrthologsFactor receptorMechanistic viewNovel EGFRDimerization
2006
EGF-independent activation of cell-surface EGF receptors harboring mutations found in gefitinib-sensitive lung cancer
Choi SH, Mendrola JM, Lemmon MA. EGF-independent activation of cell-surface EGF receptors harboring mutations found in gefitinib-sensitive lung cancer. Oncogene 2006, 26: 1567-1576. PMID: 16953218, DOI: 10.1038/sj.onc.1209957.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorTyrosine kinase domainKinase domainEGF receptorRecent structural studiesSomatic mutationsCell surface EGF receptorsTyrosine kinase activityAbsence of EGFAutoinhibitory interactionsActivation loopErbB family membersGrowth factor receptorTyrosine phosphorylationEGFR tyrosine kinase domainKinase activityNull backgroundMechanistic basisOncogenic mutationsBiochemical propertiesCell surfaceCell lung carcinoma patientsFactor receptorMutationsLung carcinoma patients
2004
Rapid Visual Assays of Oncogenic Aberrant ErbB Receptor Activation Using Fluorescence Microscopy
Berger M, Lemmon M. Rapid Visual Assays of Oncogenic Aberrant ErbB Receptor Activation Using Fluorescence Microscopy. 2004 DOI: 10.21236/ada427040.Peer-Reviewed Original ResearchErbB receptor activationHeteromeric complexesHuman cancersReceptor tyrosine kinase familyTyrosine kinase familyCell surface receptorsErbB receptor tyrosine kinase familyErbB receptor familyGrowth factorPeptide growth factorsCell biologicalKinase familyReceptor activationGrowth of cellsBiophysical approachesEGF receptorErbB2/HERReceptor familyFluorescence microscopyMajor targetClinical trialsPhysiologic outcomesReceptorsChemotherapeutic agentsFamily