Featured Publications
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 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
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
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 effectsProofreadingPhosphataseInternalization
2015
Multistrip 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
Refinement 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
2008
Detection of the active components of calf thymus nuclear proteins (TNP), histones that are binding with high affinity to HIV-1 envelope proteins and CD4 molecules.
Mamikonyan G, Kiyatkin A, Movsesyan N, Mkrtichyan M, Ghochikyan A, Petrushina I, Hwang J, Ichim T, Keledjian H, Agadjanyan M. Detection of the active components of calf thymus nuclear proteins (TNP), histones that are binding with high affinity to HIV-1 envelope proteins and CD4 molecules. Current HIV Research 2008, 6: 318-26. PMID: 18691030, DOI: 10.2174/157016208785132545.Peer-Reviewed Original ResearchConceptsCD4 moleculeHIV-1 receptors CD4HIV-1 envelope proteinHIV-1 patientsHIV-1 proteinsAnti-viral activityAIDS patientsClinical trialsImmune functionReceptor CD4CD4Viral entryHigh affinityEnvelope proteinPatientsViral moleculesGp120Active componentsMolecular mechanismsGel electrophoresisPossible mechanismImmunoaffinity chromatographyNuclear proteinsTandem mass spectrometryPlacebo
2007
Anti-Aβ1–11 Antibody Binds to Different β-Amyloid Species, Inhibits Fibril Formation, and Disaggregates Preformed Fibrils but Not the Most Toxic Oligomers*
Mamikonyan G, Necula M, Mkrtichyan M, Ghochikyan A, Petrushina I, Movsesyan N, Mina E, Kiyatkin A, Glabe C, Cribbs D, Agadjanyan M. Anti-Aβ1–11 Antibody Binds to Different β-Amyloid Species, Inhibits Fibril Formation, and Disaggregates Preformed Fibrils but Not the Most Toxic Oligomers*. Journal Of Biological Chemistry 2007, 282: 22376-22386. PMID: 17545160, PMCID: PMC2435219, DOI: 10.1074/jbc.m700088200.Peer-Reviewed Original Research
2004
Signal processing at the Ras circuit: what shapes Ras activation patterns?
Markevich NI, Moehren G, Demin OV, Kiyatkin A, Hoek JB, Kholodenko BN. Signal processing at the Ras circuit: what shapes Ras activation patterns? IET Systems Biology 2004, 1: 104-13. PMID: 17052120, DOI: 10.1049/sb:20045003.Peer-Reviewed Original ResearchConceptsP190 RhoGAPEpidermal growth factorActive GTP-bound stateGDP/GTP exchange factorGTP-bound stateSmall GTPase RasCellular signal transductionGTP exchange factorSystems biology approachSoluble tyrosine kinaseReceptor-mediated recruitmentSOS activationRasGAP activityRas proteinsCell fateExchange factorGTPase RasBiology approachRas mutantsSignal transductionInhibitory phosphorylationGTPase activityPlasma membraneRasGAPRegulatory mechanisms
2003
Immunization with a plant-produced colorectal cancer antigen
Verch T, Hooper D, Kiyatkin A, Steplewski Z, Koprowski H. Immunization with a plant-produced colorectal cancer antigen. Cancer Immunology, Immunotherapy 2003, 53: 92-99. PMID: 14566428, PMCID: PMC11032813, DOI: 10.1007/s00262-003-0428-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmBaculoviridaeCancer VaccinesCell Adhesion MoleculesComplement System ProteinsCytotoxicity, ImmunologicEnzyme-Linked Immunosorbent AssayEpithelial Cell Adhesion MoleculeFemaleGenetic VectorsHumansImmunizationLymphocyte ActivationMiceMice, Inbred BALB CNeoplasms, ExperimentalPlants, Genetically ModifiedT-LymphocytesTobacco Mosaic VirusConceptsSame antigenSimilar humoral immune responsesColorectal cancer antigenTumor-associated antigensHumoral immune responseGA733-2Cancer vaccinationCancer vaccinesActive immunizationColorectal cancer vaccineCancer antigensImmune responseCell culturesAntigen preparationsImmunizationAntigenSafety concernsCellular responsesVaccinationMetastasisVaccineMiceOncology
2001
Temperature Dependence of the Epidermal Growth Factor Receptor Signaling Network Can Be Accounted for by a Kinetic Model †
Moehren G, Markevich N, Demin O, Kiyatkin A, Goryanin I, Hoek JB, Kholodenko BN. Temperature Dependence of the Epidermal Growth Factor Receptor Signaling Network Can Be Accounted for by a Kinetic Model †. Biochemistry 2001, 41: 306-320. PMID: 11772030, DOI: 10.1021/bi011506c.Peer-Reviewed Original ResearchConceptsEpidermal growth factorEGF receptorEGFR kinaseDomain-mediated interactionsEGF receptor dimerizationProtein-protein interactionsRapid tyrosine phosphorylationMultiple signaling proteinsEGFR kinase activityReceptor phosphataseSignaling networksSignaling proteinsProtein interactionsPhosphorylation patternTyrosine phosphorylationReceptor dimerizationKinase activityTarget proteinsMembrane lipidsMolecular termsDephosphorylation reactionsEGFR pathwayPhosphataseKinasePhosphorylation