Featured Publications
Glioblastoma mutations alter EGFR dimer structure to prevent ligand bias
Hu C, Leche CA, Kiyatkin A, Yu Z, Stayrook SE, Ferguson KM, Lemmon MA. Glioblastoma mutations alter EGFR dimer structure to prevent ligand bias. Nature 2022, 602: 518-522. PMID: 35140400, PMCID: PMC8857055, DOI: 10.1038/s41586-021-04393-3.Peer-Reviewed Original ResearchKinetics 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 ResearchEGFR 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 ResearchConceptsReceptor 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 agonismCross-talk between mitogenic Ras/MAPK and survival PI3K/Akt pathways: a fine balance
Aksamitiene E, Kiyatkin A, Kholodenko BN. Cross-talk between mitogenic Ras/MAPK and survival PI3K/Akt pathways: a fine balance. Biochemical Society Transactions 2012, 40: 139-146. PMID: 22260680, DOI: 10.1042/bst20110609.Peer-Reviewed Original ResearchUntangling the wires: A strategy to trace functional interactions in signaling and gene networks
Kholodenko BN, Kiyatkin A, Bruggeman FJ, Sontag E, Westerhoff HV, Hoek JB. Untangling the wires: A strategy to trace functional interactions in signaling and gene networks. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 12841-12846. PMID: 12242336, PMCID: PMC130547, DOI: 10.1073/pnas.192442699.Peer-Reviewed Original ResearchConceptsGene networksFunctional interactionMitogen-activated protein kinase cascadeProtein kinase cascadeProteomic data setsKinase cascadeCellular signalingLarge genomicsUnidentified elementsMechanistic levelCellular networkingSignalingCell systemGenomicsInteractionInteraction routesCascadeComputer-generated responsesNetwork responseCurrent methodologiesResponse
2023
Distinct interactions stabilize EGFR dimers and higher-order oligomers in cell membranes
Mudumbi K, Burns E, Schodt D, Petrova Z, Kiyatkin A, Kim L, Mangiacapre E, Ortiz-Caraveo I, Rivera Ortiz H, Hu C, Ashtekar K, Lidke K, Lidke D, Lemmon M. Distinct interactions stabilize EGFR dimers and higher-order oligomers in cell membranes. Cell Reports 2023, 43: 113603. PMID: 38117650, PMCID: PMC10835193, DOI: 10.1016/j.celrep.2023.113603.Peer-Reviewed Original Research
2020
Comparison of tyrosine kinase domain properties for the neurotrophin receptors TrkA and TrkB.
Artim SC, Kiyatkin A, Lemmon MA. Comparison of tyrosine kinase domain properties for the neurotrophin receptors TrkA and TrkB. Biochemical Journal 2020, 477: 4053-4070. PMID: 33043964, PMCID: PMC7606831, DOI: 10.1042/bcj20200695.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain-Derived Neurotrophic FactorCatalytic DomainCell DifferentiationCell ProliferationGene Knockdown TechniquesKineticsMutationNerve Growth FactorsNerve Tissue ProteinsNeuroblastomaPC12 CellsPhosphorylationProtein DomainsRatsReceptor, trkAReceptor, trkBReceptors, Growth FactorRecombinant ProteinsRNA, Small InterferingSignal Transduction
2017
Modeling of Receptor Tyrosine Kinase Signaling: Computational and Experimental Protocols
Fey D, Aksamitiene E, Kiyatkin A, Kholodenko BN. Modeling of Receptor Tyrosine Kinase Signaling: Computational and Experimental Protocols. Methods In Molecular Biology 2017, 1636: 417-453. PMID: 28730495, DOI: 10.1007/978-1-4939-7154-1_27.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesReceptor tyrosine kinase signalingMultiple cellular processesTyrosine kinase signalingCellular processesProtein phosphorylationKinase signalingNetwork biologySystems biologyTyrosine kinaseCell survivalIntegration of experimentsPowerful approachIntegrative approachBiologyComputational protocolQuantitative datasetsKinasePhosphorylationSignalingIdentification of salientApoptosisDifferentiationGlucose metabolismRegulation
2016
Three-factor models versus time series models: quantifying time-dependencies of interactions between stimuli in cell biology and psychobiology for short longitudinal data
Frank TD, Kiyatkin A, Cheong A, Kholodenko BN. Three-factor models versus time series models: quantifying time-dependencies of interactions between stimuli in cell biology and psychobiology for short longitudinal data. Mathematical Medicine And Biology A Journal Of The IMA 2016, 34: 177-191. PMID: 27079221, DOI: 10.1093/imammb/dqw001.Peer-Reviewed Original ResearchConceptsBeta-adrenoceptor agonist clenbuterolGlucocorticoid receptor systemHuman embryonic kidney 293 cellsEmbryonic kidney 293 cellsAgonist clenbuterolTumor necrosisCritical time windowExtracellular signal-regulated kinases 1Mood disordersAntagonist drugsEpidermal growth factorAnimal studiesKidney 293 cellsCell responsesSignal-regulated kinases 1Behavioral levelGrowth factorCertain antagonistsLongitudinal dataERK activationHEK293 cellsKinase 1Cellular levelTime effectsTranscriptional activityThe Dark Side of Cell Signaling: Positive Roles for Negative Regulators
Lemmon MA, Freed DM, Schlessinger J, Kiyatkin A. The Dark Side of Cell Signaling: Positive Roles for Negative Regulators. Cell 2016, 164: 1172-1184. PMID: 26967284, PMCID: PMC4830124, DOI: 10.1016/j.cell.2016.02.047.Peer-Reviewed Original ResearchConceptsCell signalingNegative regulatorGTP/GDP cycleNew cellular statesKinase/phosphataseCell surface receptorsCellular statesSignal terminationSwitch-like transitionsSuch regulatorsReceptor internalizationGDP cycleReceptor signalingSignal activationKinetic proofreadingSignalingRegulatorOnly negative effectNegative signalsPositive roleImportant roleNegative effectsProofreadingPhosphataseInternalizationBistability in the Rac1, PAK, and RhoA Signaling Network Drives Actin Cytoskeleton Dynamics and Cell Motility Switches
Byrne KM, Monsefi N, Dawson JC, Degasperi A, Bukowski-Wills JC, Volinsky N, Dobrzyński M, Birtwistle MR, Tsyganov MA, Kiyatkin A, Kida K, Finch AJ, Carragher NO, Kolch W, Nguyen LK, von Kriegsheim A, Kholodenko BN. Bistability in the Rac1, PAK, and RhoA Signaling Network Drives Actin Cytoskeleton Dynamics and Cell Motility Switches. Cell Systems 2016, 2: 38-48. PMID: 27136688, PMCID: PMC4802415, DOI: 10.1016/j.cels.2016.01.003.Peer-Reviewed Original ResearchConceptsPAK inhibitionMesenchymal breast cancer cellsCell migrationActin cytoskeleton dynamicsRho small GTPase familyRac1 activation levelsSmall GTPase familySwitch-like responsePAK family kinasesSmall chemical inhibitorsCytoskeleton dynamicsActin dynamicsGTPase familyFamily kinasesGTPase activityBistable fashionInhibitory crosstalkChemical inhibitorsBreast cancer cellsMass spectrometry-based quantitationRac1RhoACell morphologyCancer cellsPAK
2015
Silence on the relevant literature and errors in implementation
Bastiaens P, Birtwistle MR, Blüthgen N, Bruggeman FJ, Cho KH, Cosentino C, de la Fuente A, Hoek JB, Kiyatkin A, Klamt S, Kolch W, Legewie S, Mendes P, Naka T, Santra T, Sontag E, Westerhoff HV, Kholodenko BN. Silence on the relevant literature and errors in implementation. Nature Biotechnology 2015, 33: 336-339. PMID: 25850052, DOI: 10.1038/nbt.3185.Peer-Reviewed Original ResearchMultistrip Western Blotting: A Tool for Comparative Quantitative Analysis of Multiple Proteins
Aksamitiene E, Hoek JB, Kiyatkin A. Multistrip Western Blotting: A Tool for Comparative Quantitative Analysis of Multiple Proteins. Methods In Molecular Biology 2015, 1312: 197-226. PMID: 26044004, DOI: 10.1007/978-1-4939-2694-7_23.Peer-Reviewed Original Research
2013
Kinetochore kinesin CENP-E is a processive bi-directional tracker of dynamic microtubule tips
Gudimchuk N, Vitre B, Kim Y, Kiyatkin A, Cleveland DW, Ataullakhanov FI, Grishchuk EL. Kinetochore kinesin CENP-E is a processive bi-directional tracker of dynamic microtubule tips. Nature Cell Biology 2013, 15: 1079-1088. PMID: 23955301, PMCID: PMC3919686, DOI: 10.1038/ncb2831.Peer-Reviewed Original ResearchConceptsDynamic microtubule endsMicrotubule endsMicrotubule tipsKinetochore kinesin CENPCENP-E motorDynamic microtubule tipsSingle-molecule approachVertebrate mitosisSpindle microtubulesTail domainCENPStable associationKinetochoresPlus endsChromosomesMolecular frameworkCentromeresMitosisMicrotubulesTransportersMotor mechanismsStability of attachmentVitroActive roleComputational modellingRefinement of a DNA based Alzheimer disease epitope vaccine in rabbits
Ghochikyan A, Davtyan H, Petrushina I, Hovakimyan A, Movsesyan N, Davtyan A, Kiyatkin A, Cribbs D, Agadjanyan M. Refinement of a DNA based Alzheimer disease epitope vaccine in rabbits. Human Vaccines & Immunotherapeutics 2013, 9: 1002-1010. PMID: 23399748, PMCID: PMC3899134, DOI: 10.4161/hv.23875.Peer-Reviewed Original ResearchConceptsDNA epitope vaccineEpitope vaccineTh epitopesAlzheimer's diseaseStrong humoral immune responseHumoral immune responseB-cell epitopesΒ-amyloid peptideN-terminal aspartic acidDNA vaccinePoor immunogenicityAD therapyHuman β-amyloid peptideImmune responseAD casesBrain sectionsCell epitopesEfficacy studiesVaccineEx vivoRhesus monkeysImmunogenicityShort amyloidEpitopesRabbitsImmunogenicity, Efficacy, Safety, and Mechanism of Action of Epitope Vaccine (Lu AF20513) for Alzheimer's Disease: Prelude to a Clinical Trial
Davtyan H, Ghochikyan A, Petrushina I, Hovakimyan A, Davtyan A, Poghosyan A, Marleau AM, Movsesyan N, Kiyatkin A, Rasool S, Larsen AK, Madsen PJ, Wegener KM, Ditlevsen DK, Cribbs DH, Pedersen LO, Agadjanyan MG. Immunogenicity, Efficacy, Safety, and Mechanism of Action of Epitope Vaccine (Lu AF20513) for Alzheimer's Disease: Prelude to a Clinical Trial. Journal Of Neuroscience 2013, 33: 4923-4934. PMID: 23486963, PMCID: PMC3634356, DOI: 10.1523/jneurosci.4672-12.2013.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnalysis of VarianceAnimalsAntibodies, Anti-IdiotypicAntibody FormationBrainCells, CulturedCytokinesDisease Models, AnimalDose-Response Relationship, ImmunologicEnzyme-Linked Immunosorbent AssayEpitopes, B-LymphocyteEpitopes, T-LymphocyteFemaleGuinea PigsHumansImmunologic MemoryMacaca fascicularisMaleMiceMice, TransgenicMutationNeurogliaPeptide FragmentsPlaque, AmyloidProtein BindingSurface Plasmon ResonanceT-LymphocytesVaccinationVaccinesConceptsAnti-Aβ antibodiesMemory T helper cellsT cell responsesT helper cellsClinical trialsMild ADDisease processAutoreactive T cell responsesAD mouse modelAD-like pathologyCerebral amyloid angiopathyRecent clinical trialsTetanus toxoid vaccineStrong humoral immunityStrong humoral responseAlzheimer's disease processNeurotoxic Aβ peptidesMechanism of actionMicroglial activationAmyloid angiopathyImmunotherapeutic approachesSingle immunizationHumoral immunityHumoral responseToxoid vaccine
2012
Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise
Birtwistle MR, Rauch J, Kiyatkin A, Aksamitiene E, Dobrzyński M, Hoek JB, Kolch W, Ogunnaike BA, Kholodenko BN. Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise. BMC Systems Biology 2012, 6: 109. PMID: 22920937, PMCID: PMC3484110, DOI: 10.1186/1752-0509-6-109.Peer-Reviewed Original ResearchConceptsProtein expression noiseSingle-cell signalingExtracellular signal-regulated kinaseExpression noiseCell variabilityEpidermal growth factor stimulationProtein abundance variationCell fate decisionsPopulation responsesGrowth factor stimulationSingle cellsSignal-regulated kinaseCell population levelProtein expressionSingle-cell levelERK pathway activationFate decisionsPopulation levelFactor stimulationCell signalingCell population responseERK responseBiological outcomesPathway activationCell levelP1‐306: Translational study: Refinement of DNA‐based Alzheimer's disease (AD) epitope vaccine in rabbits
Davtyan H, Ghochikyan A, Petrushina I, Hovakimyan A, Movsesyan N, Kiyatkin A, Hannaman D, Evans C, Cribbs D, Agadjanyan M. P1‐306: Translational study: Refinement of DNA‐based Alzheimer's disease (AD) epitope vaccine in rabbits. Alzheimer's & Dementia 2012, 8: p211-p211. DOI: 10.1016/j.jalz.2012.05.587.Peer-Reviewed Original Research
2011
Prolactin-stimulated activation of ERK1/2 mitogen-activated protein kinases is controlled by PI3-kinase/Rac/PAK signaling pathway in breast cancer cells
Aksamitiene E, Achanta S, Kolch W, Kholodenko BN, Hoek JB, Kiyatkin A. Prolactin-stimulated activation of ERK1/2 mitogen-activated protein kinases is controlled by PI3-kinase/Rac/PAK signaling pathway in breast cancer cells. Cellular Signalling 2011, 23: 1794-1805. PMID: 21726627, PMCID: PMC3156300, DOI: 10.1016/j.cellsig.2011.06.014.Peer-Reviewed Original ResearchMeSH KeywordsBreastBreast NeoplasmsCell Line, TumorFemaleGene Expression Regulation, NeoplasticGene SilencingHumansImmunoprecipitationMitogen-Activated Protein KinasesP21-Activated KinasesPhosphatidylinositol 3-KinasesPhosphorylationProlactinProtein BindingProto-Oncogene Proteins c-aktReal-Time Polymerase Chain ReactionRNA, Small InterferingSignal TransductionTransfectionConceptsBreast cancer cellsExtracellular signal-regulated kinases ERK1PI3-kinase/Akt pathwayDistinct signal transduction pathwaysERK1/2 mitogen-activated protein kinasesRac/PAK pathwayCancer cellsMitogen-activated protein kinaseSignal transduction pathwaysKinase/AktPDK1/AktJAK/STATSiRNA-mediated suppressionMAPK/ERKJAK2/STAT5MAPK signaling pathwaysRegulatory circuitsFAK activityKinases ERK1PAK pathwaySrc familyProtein interactionsProtein kinaseTransduction pathwaysPhosphoinositide 3THE ROUTES OF ERK ACTIVATION IN PROLACTIN‐STIMULATED BREAST CANCER CELLS
Aksamitiene E, Achanta S, Kiyatkin A, Hoek J. THE ROUTES OF ERK ACTIVATION IN PROLACTIN‐STIMULATED BREAST CANCER CELLS. The FASEB Journal 2011, 25: 946.1-946.1. DOI: 10.1096/fasebj.25.1_supplement.946.1.Peer-Reviewed Original ResearchJanus kinase/signal transducerDistinct signal transduction pathwaysRac/PAK pathwayBreast cancer cellsKinase/signal transducerRas/mitogenSignal transduction pathwaysActivator of transcriptionKinase/AktTotal cell lysatesActivity of JAK2Cancer cellsPI3K/AktAdaptor proteinShc familyPAK pathwaySrc familyProtein kinaseTransduction pathwaysTyrosine phosphorylationC-RafPhosphoinositide 3Cancer cell proliferationSignal transducerMAPK signaling