2018
Impact of measurement noise, experimental design, and estimation methods on Modular Response Analysis based network reconstruction
Thomaseth C, Fey D, Santra T, Rukhlenko OS, Radde NE, Kholodenko BN. Impact of measurement noise, experimental design, and estimation methods on Modular Response Analysis based network reconstruction. Scientific Reports 2018, 8: 16217. PMID: 30385767, PMCID: PMC6212399, DOI: 10.1038/s41598-018-34353-3.Peer-Reviewed Original ResearchConceptsModular Response AnalysisNetwork reconstructionSteady-state response curvesStatistical conceptsMeasurement noisePropagation of noiseNoise settingsEstimation methodNetwork structureTerms of accuracyLarge perturbationsResponse analysisDifferent replicatesPerturbation dataRegression strategyNoise
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
2004
Quantitative analysis of signaling networks
Sauro H, Kholodenko B. Quantitative analysis of signaling networks. Progress In Biophysics And Molecular Biology 2004, 86: 5-43. PMID: 15261524, DOI: 10.1016/j.pbiomolbio.2004.03.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChemotaxisComputer SimulationComputers, MolecularFeedbackHumansMitogen-Activated Protein KinasesModels, BiologicalMultienzyme ComplexesNumerical Analysis, Computer-AssistedSignal TransductionSignaling switches and bistability arising from multisite phosphorylation in protein kinase cascades
Markevich N, Hoek J, Kholodenko B. Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades. Journal Of Cell Biology 2004, 164: 353-359. PMID: 14744999, PMCID: PMC2172246, DOI: 10.1083/jcb.200308060.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEnzyme ActivationFeedback, PhysiologicalMAP Kinase Signaling SystemMitogen-Activated Protein KinasesModels, TheoreticalPhosphorylationConceptsExtracellular signal-regulated kinaseMultisite phosphorylationProtein kinase cascadeBistable switchSignal-regulated kinaseKinase cascadeMAPK cascadeWidespread mechanismDifferent kinasesSame phosphataseProtein kinasePositive feedback loopProtein activityDephosphorylation reactionsCovalent modificationKinaseMAPK phosphorylationFeedback regulationPhosphorylationKinetic propertiesPhosphataseFeedback loopCascade