2016
Overcoming resistance to HER2 inhibitors through state-specific kinase binding
Novotny CJ, Pollari S, Park JH, Lemmon MA, Shen W, Shokat KM. Overcoming resistance to HER2 inhibitors through state-specific kinase binding. Nature Chemical Biology 2016, 12: 923-930. PMID: 27595329, PMCID: PMC5069157, DOI: 10.1038/nchembio.2171.Peer-Reviewed Original Research
2013
Mechanism for activation of mutated epidermal growth factor receptors in lung cancer
Brewer M, Yun CH, Lai D, Lemmon MA, Eck MJ, Pao W. Mechanism for activation of mutated epidermal growth factor receptors in lung cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: e3595-e3604. PMID: 24019492, PMCID: PMC3780914, DOI: 10.1073/pnas.1220050110.Peer-Reviewed Original ResearchConceptsWT epidermal growth factor receptorEpidermal growth factor receptorTyrosine kinase domainGrowth factor receptorConformational changesAsymmetric dimer interfaceMutant epidermal growth factor receptorAllosteric conformational changeAsymmetric dimer formationFactor receptorIntermolecular regulationKinase domainEGFR tyrosine kinase domainDimer interfaceMutantsM mutantActive conformation
2011
Molecular dynamics analysis of conserved hydrophobic and hydrophilic bond-interaction networks in ErbB family kinases
Shih AJ, Telesco SE, Choi SH, Lemmon MA, Radhakrishnan R. Molecular dynamics analysis of conserved hydrophobic and hydrophilic bond-interaction networks in ErbB family kinases. Biochemical Journal 2011, 436: 241-251. PMID: 21426301, PMCID: PMC3138537, DOI: 10.1042/bj20101791.Peer-Reviewed Original ResearchConceptsErbB familyDifferent molecular contextsIntracellular kinase domainImportant regulatory elementsSrc kinase HckReceptor tyrosine kinasesHomologous receptor tyrosine kinasesSequence similarityKinase domainRegulatory elementsDimer interfaceSubdomain motionsInactive conformationKey residuesEGFR activationMolecular contextTyrosine kinasePresent molecular dynamics studyBond networkActive conformationConformational statesKinaseErbB kinasesMolecular dynamics analysisSalt bridge
2009
ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor
Alvarado D, Klein DE, Lemmon MA. ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor. Nature 2009, 461: 287-291. PMID: 19718021, PMCID: PMC2762480, DOI: 10.1038/nature08297.Peer-Reviewed Original Research
2008
Mechanism 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
2006
Essential Role for Rac in Heregulin β1 Mitogenic Signaling: a Mechanism That Involves Epidermal Growth Factor Receptor and Is Independent of ErbB4
Yang C, Liu Y, Lemmon MA, Kazanietz MG. Essential Role for Rac in Heregulin β1 Mitogenic Signaling: a Mechanism That Involves Epidermal Growth Factor Receptor and Is Independent of ErbB4. Molecular And Cellular Biology 2006, 26: 831-842. PMID: 16428439, PMCID: PMC1347034, DOI: 10.1128/mcb.26.3.831-842.2006.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, BlockingBreast NeoplasmsCell MovementCell ProliferationEnzyme ActivationErbB ReceptorsFemaleHumansNeoplasm ProteinsNeuregulin-1Phosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktReceptor, ErbB-2Receptor, ErbB-3Receptor, ErbB-4RNA InterferenceSrc-Family KinasesTumor Cells, CulturedConceptsExtracellular signal-regulated kinaseHeregulin beta1RNA interferenceBreast cancer cellsCancer cellsActin cytoskeleton reorganizationDepletion of Rac1Activation of RacInactivation of RacTransactivation of EGFRSignal-regulated kinaseErbB receptor inhibitorsEpidermal growth factor receptorRho GTPasesMitogenic signalingRac activationRac GTPaseEpidermal growth factorGrowth factor receptorCytoskeleton reorganizationDownstream effectorsMitogenic activityCancer cell proliferationERK activationBreast cancer cell proliferation
2001
The Single Transmembrane Domains of ErbB Receptors Self-associate in Cell Membranes*
Mendrola JM, Berger MB, King MC, Lemmon MA. The Single Transmembrane Domains of ErbB Receptors Self-associate in Cell Membranes*. Journal Of Biological Chemistry 2001, 277: 4704-4712. PMID: 11741943, DOI: 10.1074/jbc.m108681200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceCell MembraneChloramphenicol O-AcetyltransferaseDimerizationDNA Mutational AnalysisErbB ReceptorsEscherichia coliGenetic VectorsGlutamic AcidHumansLigandsMaltoseModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedMutationProtein Structure, TertiaryReceptor Protein-Tyrosine KinasesReceptor, ErbB-2Receptor, ErbB-3Receptor, ErbB-4Recombinant Fusion ProteinsSequence Homology, Amino AcidValineConceptsTM domain interactionsTM domainReceptor tyrosine kinasesEpidermal growth factor receptorGrowth factor receptorDomain interactionsSingle transmembrane alpha-helixReceptor dimersTyrosine kinaseExtracellular domainErbB receptor functionEscherichia coli cell membraneSingle transmembrane domainTransmembrane alpha-helixErbB receptorsCell membraneLimited mutational analysisFactor receptorGlutamic acid mutationTransmembrane domainGxxxG motifDomain dimerMutational analysisAlpha-helixErythropoietin receptor
2000
Extracellular domains drive homo‐ but not hetero‐dimerization of erbB receptors
Ferguson K, Darling P, Mohan M, Macatee T, Lemmon M. Extracellular domains drive homo‐ but not hetero‐dimerization of erbB receptors. The EMBO Journal 2000, 19: 4632-4643. PMID: 10970856, PMCID: PMC302059, DOI: 10.1093/emboj/19.17.4632.Peer-Reviewed Original Research
1997
Dimerization of the p185neu transmembrane domain is necessary but not sufficient for transformation
Burke C, Lemmon M, Coren B, Engelman D, Stern D. Dimerization of the p185neu transmembrane domain is necessary but not sufficient for transformation. Oncogene 1997, 14: 687-696. PMID: 9038376, DOI: 10.1038/sj.onc.1200873.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesTransmembrane domainEpidermal growth factor receptorSignal transductionWild-type domainSecond-site mutationsPosition 664Dimerization domainGrowth factor receptorTyrosine kinaseGlycophorin AFactor receptorValine substitutionDimerizationMutationsTransductionGlutamic acidDomainWeak dimerizationMutantsKinaseSignalingProteinEGFChimeras