Featured Publications
Scaffolding Protein Grb2-associated Binder 1 Sustains Epidermal Growth Factor-induced Mitogenic and Survival Signaling by Multiple Positive Feedback Loops*
Kiyatkin A, Aksamitiene E, Markevich NI, Borisov NM, Hoek JB, Kholodenko BN. Scaffolding Protein Grb2-associated Binder 1 Sustains Epidermal Growth Factor-induced Mitogenic and Survival Signaling by Multiple Positive Feedback Loops*. Journal Of Biological Chemistry 2006, 281: 19925-19938. PMID: 16687399, PMCID: PMC2312093, DOI: 10.1074/jbc.m600482200.Peer-Reviewed Original ResearchConceptsEpidermal growth factorRas/MAPK signalingGab1 tyrosine phosphorylationGrowth factorRole of Gab1PI3K/Akt activationMultiple positive feedback loopsProtein Grb2Mutant proteinsScaffold proteinTyrosine phosphorylationBinder 1Positive feedback loopMitogenic pathwaysMAPK signalingEssential functionsSurvival signalingDiverse perturbationsCellular responsesAkt activationCytokine receptorsPharmacological inhibitorsGab1EGF dosesGrb2
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 activity
2015
Signalling mechanisms regulating phenotypic changes in breast cancer cells
Volinsky N, McCarthy CJ, von Kriegsheim A, Saban N, Okada-Hatakeyama M, Kolch W, Kholodenko BN. Signalling mechanisms regulating phenotypic changes in breast cancer cells. Bioscience Reports 2015, 35: e00178. PMID: 25643809, PMCID: PMC4370098, DOI: 10.1042/bsr20140172.Peer-Reviewed Original ResearchConceptsCell fate decisionsATP-citrate lyaseFate decisionsPhenotypic changesBreast cancer cellsEpidermal growth factorCell fate decision processesCancer cellsLipid accumulationIrreversible phenotypic changesPhosphoinositide-3 kinaseSimilar cellular responsesPI3K pathwayGrowth factorRapamycin complexKinase pathwayNegative regulatorMolecular mechanismsCellular responsesMetabolic pathwaysMammalian targetK pathwayCitrate lyaseLipogenic pathwayCell proliferation
2009
Systems‐level interactions between insulin–EGF networks amplify mitogenic signaling
Borisov N, Aksamitiene E, Kiyatkin A, Legewie S, Berkhout J, Maiwald T, Kaimachnikov NP, Timmer J, Hoek JB, Kholodenko BN. Systems‐level interactions between insulin–EGF networks amplify mitogenic signaling. Molecular Systems Biology 2009, 5: msb200919. PMID: 19357636, PMCID: PMC2683723, DOI: 10.1038/msb.2009.19.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingCell LineDose-Response Relationship, DrugDrug SynergismEnzyme ActivationEpidermal Growth FactorGRB2 Adaptor ProteinHumansImmunoprecipitationInsulinMitogen-Activated Protein KinasesMitogensModels, BiologicalPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Kinase InhibitorsProtein Tyrosine Phosphatase, Non-Receptor Type 11Ras ProteinsReproducibility of ResultsSignal TransductionSrc-Family KinasesSystems BiologyConceptsInsulin receptor substrateEpidermal growth factorRas/ERK cascadeCrosstalk mechanismsComplex cellular responsesPhosphatase SHP2Mitogenic signalingERK cascadeSrc kinaseReceptor substrateERK activityRaf levelsInsulin-induced increaseERK activationCellular responsesGab1HEK293 cellsExternal cuesEGF dosesPoor activatorGrowth factorMitogenicMitogenic responseComputational approachSHP2
2007
Ligand‐dependent responses of the ErbB signaling network: experimental and modeling analyses
Birtwistle MR, Hatakeyama M, Yumoto N, Ogunnaike BA, Hoek JB, Kholodenko BN. Ligand‐dependent responses of the ErbB signaling network: experimental and modeling analyses. Molecular Systems Biology 2007, 3: msb4100188. PMID: 18004277, PMCID: PMC2132449, DOI: 10.1038/msb4100188.Peer-Reviewed Original ResearchMeSH KeywordsAndrostadienesButadienesCell Line, TumorCell MembraneDimerizationEnzyme ActivationEpidermal Growth FactorExtracellular Signal-Regulated MAP KinasesFeedback, PhysiologicalHumansLigandsModels, BiologicalNeuregulin-1NitrilesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Structure, TertiaryProto-Oncogene Proteins c-aktReceptor Protein-Tyrosine KinasesReproducibility of ResultsSignal TransductionWortmanninConceptsEpidermal growth factorERK activityEGF-induced signalingMultiple human cancersPhosphoinositol-3 kinaseLigand-dependent responsesSustained signalingERK activationDownstream proteinsAkt activationInhibitor U0126Major regulatorHuman cancersErbB receptorsLigand dosesHeregulinErbBKinaseSignalingGrowth factorActivationKey roleU0126AktRegulator
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
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