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 ResearchConceptsGene networksFunctional interactionMitogen-activated protein kinase cascadeProtein kinase cascadeProteomic data setsKinase cascadeCellular signalingLarge genomicsUnidentified elementsMechanistic levelCellular networkingSignalingCell systemGenomicsInteractionInteraction routesCascadeComputer-generated responsesNetwork responseCurrent methodologiesResponse
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 ResearchConceptsExtracellular signal-regulated kinaseMultisite phosphorylationProtein kinase cascadeBistable switchSignal-regulated kinaseKinase cascadeMAPK cascadeWidespread mechanismDifferent kinasesSame phosphataseProtein kinasePositive feedback loopProtein activityDephosphorylation reactionsCovalent modificationKinaseMAPK phosphorylationFeedback regulationPhosphorylationKinetic propertiesPhosphataseFeedback loopCascade
2002
Modular Response Analysis of Cellular Regulatory Networks
BRUGGEMAN F, WESTERHOFF H, HOEK J, KHOLODENKO B. Modular Response Analysis of Cellular Regulatory Networks. Journal Of Theoretical Biology 2002, 218: 507-520. PMID: 12384053, DOI: 10.1006/jtbi.2002.3096.Peer-Reviewed Original ResearchConceptsRegulatory networksMitogen-activated protein kinase cascadeEpidermal growth factor receptor (EGFR) networkGrowth factor receptor networkProtein kinase cascadeIntermodular interactionsCellular regulatory networksModular Response AnalysisIntracellular regulatory networksAmmonium assimilationKinase cascadeMolecular biological analysisGenetic circuitsInteraction mapSignal transducingEscherichia coliReceptor networkModular organizationMolecular interactionsBiological analysisSignal transferColiTransducingRegulationInteractionMAP kinase cascade signaling and endocytic trafficking: a marriage of convenience?
Kholodenko BN. MAP kinase cascade signaling and endocytic trafficking: a marriage of convenience? Trends In Cell Biology 2002, 12: 173-177. PMID: 11978536, DOI: 10.1016/s0962-8924(02)02251-1.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinase cascadeMembrane-bound kinaseSlow protein diffusionProtein kinase cascadeInhibitors of endocytosisTarget phosphoproteinsEffective signal transductionCytosolic phosphataseEndocytic traffickingKinase cascadePhosphorylation signalsSignal transductionEndocytic vesiclesRapid dephosphorylationMAP kinaseCascade signalingMAPK activationProtein diffusionMolecular motorsKinaseTraffickingProteinActive transportAdditional mechanismSuch gradients