Featured Publications
Untangling 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 ResearchMeSH KeywordsAnimalsMAP Kinase Signaling SystemModels, BiologicalModels, TheoreticalProtein BindingProtein KinasesSignal TransductionConceptsGene networksFunctional interactionMitogen-activated protein kinase cascadeProtein kinase cascadeProteomic data setsKinase cascadeCellular signalingLarge genomicsUnidentified elementsMechanistic levelCellular networkingSignalingCell systemGenomicsInteractionInteraction routesCascadeComputer-generated responsesNetwork responseCurrent methodologiesResponse
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
2013
Immunogenicity, 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
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 3
2009
Molecular Dynamics Simulations Reveal that Tyr-317 Phosphorylation Reduces Shc Binding Affinity for Phosphotyrosyl Residues of Epidermal Growth Factor Receptor
Suenaga A, Hatakeyama M, Kiyatkin AB, Radhakrishnan R, Taiji M, Kholodenko BN. Molecular Dynamics Simulations Reveal that Tyr-317 Phosphorylation Reduces Shc Binding Affinity for Phosphotyrosyl Residues of Epidermal Growth Factor Receptor. Biophysical Journal 2009, 96: 2278-2288. PMID: 19289054, PMCID: PMC2717265, DOI: 10.1016/j.bpj.2008.11.018.Peer-Reviewed Original ResearchConceptsSrc homology 2Epidermal growth factor receptorGrowth factor receptorPhospho-tyrosine binding (PTB) domainsLinker regionFull-length ShcPhospho-tyrosine residuesKey conformational changesFactor receptorShc interactionTyr-317Protein ShcTyrosine kinase receptorsPhosphorylated ShcPTB domainRas-mitogenHomology 2Phosphorylation resultsPhosphotyrosyl peptidesProtein kinaseTyrosine phosphorylationBinding domainsSubsequent phosphorylationPhosphotyrosyl residuesShc
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