2021
Computational studies of anaplastic lymphoma kinase mutations reveal common mechanisms of oncogenic activation
Patil K, Jordan EJ, Park JH, Suresh K, Smith CM, Lemmon AA, Mossé YP, Lemmon MA, Radhakrishnan R. Computational studies of anaplastic lymphoma kinase mutations reveal common mechanisms of oncogenic activation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2019132118. PMID: 33674381, PMCID: PMC7958353, DOI: 10.1073/pnas.2019132118.Peer-Reviewed Original ResearchMeSH KeywordsAnaplastic Lymphoma KinaseEnzyme ActivationHumansMachine LearningMolecular Dynamics SimulationMutationProtein Conformation, alpha-Helical
2020
Kinetics of receptor tyrosine kinase activation define ERK signaling dynamics
Kiyatkin A, van Alderwerelt van Rosenburgh IK, Klein DE, Lemmon MA. Kinetics of receptor tyrosine kinase activation define ERK signaling dynamics. Science Signaling 2020, 13 PMID: 32817373, PMCID: PMC7521189, DOI: 10.1126/scisignal.aaz5267.Peer-Reviewed Original Research
2012
Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family
Artim SC, Mendrola JM, Lemmon MA. Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family. Biochemical Journal 2012, 448: 213-220. PMID: 22992069, PMCID: PMC3492919, DOI: 10.1042/bj20121365.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAntigens, CDCatalytic DomainCrystallography, X-RayEnzyme ActivationHumansIn Vitro TechniquesModels, MolecularMutationNeoplasmsProtein Structure, QuaternaryReceptor Tyrosine Kinase-like Orphan ReceptorsReceptor, InsulinReceptor, trkARecombinant Proteins
2010
Cell Signaling by Receptor Tyrosine Kinases
Lemmon MA, Schlessinger J. Cell Signaling by Receptor Tyrosine Kinases. Cell 2010, 141: 1117-1134. PMID: 20602996, PMCID: PMC2914105, DOI: 10.1016/j.cell.2010.06.011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEnzyme ActivationHumansNeoplasmsReceptor Protein-Tyrosine KinasesSignal TransductionConceptsReceptor tyrosine kinasesTyrosine kinaseIntracellular tyrosine kinase domainRecent structural studiesGrowth factor ligandsTyrosine kinase domainUnexpected diversityKinase domainCell signalingLigand bindingCellular responsesFactor ligandRTK mutationsKinaseStructural studiesActivationSignalingDiversityMutationsDimerizationMechanismBindingDomain
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 ResearchRole of Inn1 and its interactions with Hof1 and Cyk3 in promoting cleavage furrow and septum formation in S. cerevisiae
Nishihama R, Schreiter JH, Onishi M, Vallen EA, Hanna J, Moravcevic K, Lippincott MF, Han H, Lemmon MA, Pringle JR, Bi E. Role of Inn1 and its interactions with Hof1 and Cyk3 in promoting cleavage furrow and septum formation in S. cerevisiae. Journal Of Cell Biology 2009, 185: 995-1012. PMID: 19528296, PMCID: PMC2711614, DOI: 10.1083/jcb.200903125.Peer-Reviewed Original ResearchConceptsCleavage furrowChitin synthase Chs2C-terminal regionActomyosin ring contractionCytokinesis proteinsDivision siteMitotic exitPXXP motifSH3 domainSeptum formationC2 domainS. cerevisiaePlasma membraneBind phospholipidsAMR contractionN-terminusCyk3Inn1Extracellular matrixChs2ProteinImportant interactionsHof1MembraneCytokinesis
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
2000
The Role of the Pleckstrin Homology Domain in Membrane Targeting and Activation of Phospholipase Cβ1 *
Razzini G, Brancaccio A, Lemmon M, Guarnieri S, Falasca M. The Role of the Pleckstrin Homology Domain in Membrane Targeting and Activation of Phospholipase Cβ1 *. Journal Of Biological Chemistry 2000, 275: 14873-14881. PMID: 10809731, DOI: 10.1074/jbc.275.20.14873.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAndrostadienesAnimalsCell MembraneChromonesCOS CellsCulture Media, Serum-FreeEnzyme ActivationEnzyme InhibitorsGlutathione TransferaseGreen Fluorescent ProteinsGrowth SubstancesGTP-Binding ProteinsHeLa CellsHumansIsoenzymesLuminescent ProteinsMiceMicroscopy, ConfocalMicroscopy, FluorescenceMorpholinesPhosphatidylinositolsPhospholipase C betaPolymerase Chain ReactionRatsRecombinant Fusion ProteinsSrc Homology DomainsTransfectionType C PhospholipasesWortmanninConceptsPlasma membrane localizationPleckstrin homology domainMembrane localizationSerum-starved cellsPlasma membraneMembrane targetingLysophosphatidic acidHomology domainGreen fluorescent protein fusion proteinFluorescent protein fusion proteinProtein fusion proteinIsolated PH domainActivation of PLCbetaStimulation of cellsPH domainPhospholipase Cβ1Gbetagamma subunitsBetagamma subunitsAmino terminusWortmannin pretreatmentFusion proteinG proteinsActivation of phospholipaseFluorescence microscopyPhosphoinositide