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
2016
HER2-HER3 dimer quantification by FLIM-FRET predicts breast cancer metastatic relapse independently of HER2 IHC status
Weitsman G, Barber PR, Nguyen LK, Lawler K, Patel G, Woodman N, Kelleher MT, Pinder SE, Rowley M, Ellis PA, Purushotham AD, Coolen AC, Kholodenko BN, Vojnovic B, Gillett C, Ng T. HER2-HER3 dimer quantification by FLIM-FRET predicts breast cancer metastatic relapse independently of HER2 IHC status. Oncotarget 2016, 7: 51012-51026. PMID: 27618787, PMCID: PMC5239455, DOI: 10.18632/oncotarget.9963.Peer-Reviewed Original ResearchConceptsGroup of patientsMetastatic relapsePredictive biomarkersHER2 proteinHER2 IHC statusOnly predictive biomarkerInvasive breast cancerNovel prognostic biomarkerOverexpression of HER2Important prognostic markerBreast cancer tissuesHistology-based analysisSignificant clinical utilityHER2-HER3 dimersIHC statusHER2 expressionTissue microarray coresPrognostic markerBreast cancerPrognostic biomarkerHER2-HER3 heterodimersClinical utilityCancer tissuesTumor progressionDriver of proliferation
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 ResearchGene Regulatory NetworksModels, Theoretical
2004
Signaling 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
1998
Metabolic design: How to engineer a living cell to desired metabolite concentrations and fluxes
Kholodenko B, Cascante M, Hoek J, Westerhoff H, Schwaber J. Metabolic design: How to engineer a living cell to desired metabolite concentrations and fluxes. Biotechnology And Bioengineering 1998, 59: 239-247. PMID: 10099334, DOI: 10.1002/(sici)1097-0290(19980720)59:2<239::aid-bit11>3.0.co;2-9.Peer-Reviewed Original Research
1996
Paradoxical control properties of enzymes within pathways: can activation cause an enzyme to have increased control?
KHOLODENKO B, BROWN G. Paradoxical control properties of enzymes within pathways: can activation cause an enzyme to have increased control? Biochemical Journal 1996, 314: 753-760. PMID: 8615766, PMCID: PMC1217121, DOI: 10.1042/bj3140753.Peer-Reviewed Original Research
1995
Control analysis of transit time for free and enzyme-bound metabolites: physiological and evolutionary significance of metabolic response times
Cascante M, Meléndez-Hevia E, Kholodenko B, Sicilia J, Kacser H. Control analysis of transit time for free and enzyme-bound metabolites: physiological and evolutionary significance of metabolic response times. Biochemical Journal 1995, 308: 895-899. PMID: 8948448, PMCID: PMC1136808, DOI: 10.1042/bj3080895.Peer-Reviewed Original Research
1994
Control by Enzymes, Coenzymes and Conserved Moieties
Kholodenko B, Sauro H, Westerhoff H. Control by Enzymes, Coenzymes and Conserved Moieties. The FEBS Journal 1994, 225: 179-186. PMID: 7925436, DOI: 10.1111/j.1432-1033.1994.00179.x.Peer-Reviewed Original Research
1992
Control of the metabolic flux in a system with high enzyme concentrations and moiety‐conserved cycles
KHOLODENKO B, LYUBAREV A, KURGANOV B. Control of the metabolic flux in a system with high enzyme concentrations and moiety‐conserved cycles. The FEBS Journal 1992, 210: 147-153. PMID: 1446668, DOI: 10.1111/j.1432-1033.1992.tb17402.x.Peer-Reviewed Original ResearchEnzymesModels, Theoretical