2009
Four‐dimensional dynamics of MAPK information‐processing systems
Kholodenko BN, Birtwistle MR. Four‐dimensional dynamics of MAPK information‐processing systems. WIREs Mechanisms Of Disease 2009, 1: 28-44. PMID: 20182652, PMCID: PMC2826817, DOI: 10.1002/wsbm.16.Peer-Reviewed Original ResearchConceptsMultiple target proteinsMyriad of stimuliCell surface receptorsMAPK cascadeActive kinasePhosphorylation signalsProtein phosphorylationCellular outcomesCytosolic localizationProtein kinaseEndocytotic traffickingPlasma membraneProtein activityTarget proteinsMembrane confinementXenopus eggsToggle switchKinaseMolecular motorsIntracellular gradientsSpatio-temporal guidanceLarge cellsFour-dimensional dynamicsPhosphorylationTrafficking
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
2000
Diffusion control of protein phosphorylation in signal transduction pathways
KHOLODENKO B, BROWN G, HOEK J. Diffusion control of protein phosphorylation in signal transduction pathways. Biochemical Journal 2000, 350: 901-907. PMID: 10970807, PMCID: PMC1221325, DOI: 10.1042/bj3500901.Peer-Reviewed Original ResearchConceptsProtein phosphorylationProtein kinasePhosphorylation fluxProtein diffusionSignal transduction pathwaysProtein phosphataseSpherical cellsTransduction pathwaysDifferent cellular geometriesCellular locationPlasma membranePlanar membranesKinaseCell membraneCellular geometryProtein diffusion coefficientsPhosphatasePhosphorylationCell centerProteinMembraneCellsSpatial gradientsCytoplasmPathwayWhy cytoplasmic signalling proteins should be recruited to cell membranes
Kholodenko B, Hoek J, Westerhoff H, Kholodenko B, Hoek J, Westerhoff H. Why cytoplasmic signalling proteins should be recruited to cell membranes. Trends In Cell Biology 2000, 10: 173-178. PMID: 10754559, DOI: 10.1016/s0962-8924(00)01741-4.Peer-Reviewed Original ResearchConceptsSignal transduction proteinsSignal transduction chainTransduction proteinsCytoplasmic signaling proteinsMembrane localizationAdaptor proteinSignaling proteinsMembrane proteinsSignal transductionPlasma membraneRate of encounterImportant structural constraintsCell membraneProteinExtent of activationMembraneNumber of complexesDownstream processesActivationLocalizationTransductionReceptorsStructural constraintsLow concentrationsComplexes
1999
Spatial gradients of cellular phospho‐proteins
Brown G, Kholodenko B. Spatial gradients of cellular phospho‐proteins. FEBS Letters 1999, 457: 452-454. PMID: 10471827, DOI: 10.1016/s0014-5793(99)01058-3.Peer-Reviewed Original ResearchConceptsCellular signalingProtein kinaseDifferent cellular geometriesCellular locationPlasma membranePhosphorylated formPlanar membranesProtein diffusionPhosphatase activityKinaseCellular geometryProtein diffusion coefficientsSpatial gradientsSpherical cellsProteinMembraneSuch gradientsCellsSignalingCytoplasmPhosphataseImportant implicationsGradientPotential size
1996
Direct Transfer of Control and Multidrug Resistance
Westerhoff H, Rohwer J, Heijn M, Mülder S, Ghauharali R, Wielinga P, Kholodenko B, Spoelstra E, Lankelma J. Direct Transfer of Control and Multidrug Resistance. NATO Science Series A: 1996, 283-292. DOI: 10.1007/978-1-4615-5845-3_29.Peer-Reviewed Original ResearchPhosphotransferase systemIntact cellsBacterial phosphotransferase systemPlasma membrane vesiclesCellular processesPTS enzymesSignal transductionPlasma membraneKinetic propertiesMultidrug pumpMembrane vesiclesIntracellular daunorubicin concentrationMultidrug resistanceIntricate organizationP-glycoproteinModel systemIntact systemDrug effluxDrug pumpCellsPassive permeabilityDirect transferTransductionDistribution of controlDNA