2013
Control of the G- protein cascade dynamics by GDP dissociation inhibitors
Nikonova E, Tsyganov MA, Kolch W, Fey D, Kholodenko BN. Control of the G- protein cascade dynamics by GDP dissociation inhibitors. Molecular Omics 2013, 9: 2454-2462. PMID: 23872884, DOI: 10.1039/c3mb70152b.Peer-Reviewed Original ResearchConceptsGDP dissociation inhibitorGuanine nucleotide exchange factorsRho family GTPasesDissociation inhibitorNucleotide exchange factorsKey cellular processesProtrusion-retraction cyclesSignal-induced changesCell migration behaviorActive GTPExchange factorInactive GDPCellular processesGTPase activityRac1 activityGTPasesBistable switchRhoADistinct modesRhoGDI1GTPaseInhibitorsRac1GTPCytoplasm
2009
Toggle switches, pulses and oscillations are intrinsic properties of the Src activation/deactivation cycle
Kaimachnikov NP, Kholodenko BN. Toggle switches, pulses and oscillations are intrinsic properties of the Src activation/deactivation cycle. The FEBS Journal 2009, 276: 4102-4118. PMID: 19627364, PMCID: PMC2924194, DOI: 10.1111/j.1742-4658.2009.07117.x.Peer-Reviewed Original Research
2005
Signaling through Receptors and Scaffolds: Independent Interactions Reduce Combinatorial Complexity
Borisov N, Markevich N, Hoek J, Kholodenko B. Signaling through Receptors and Scaffolds: Independent Interactions Reduce Combinatorial Complexity. Biophysical Journal 2005, 89: 951-966. PMID: 15923229, PMCID: PMC1366644, DOI: 10.1529/biophysj.105.060533.Peer-Reviewed Original ResearchConceptsProtein complexesComplex signaling networksDistinct physiological responsesSignaling networksAdaptor proteinDocking siteMolecular eventsTemporal dynamicsPhysiological responsesDistinct sitesIndependent interactionsBranched networkSeparate domainsMolecular speciesDomain-oriented approachCombinatorial increaseReceptorsIndividual sitesSitesComplexesScaffoldsSpeciesTens of thousandsProteinDifferent sites
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
2002
Control Analysis for Autonomously Oscillating Biochemical Networks
Reijenga K, Westerhoff H, Kholodenko B, Snoep J. Control Analysis for Autonomously Oscillating Biochemical Networks. Biophysical Journal 2002, 82: 99-108. PMID: 11751299, PMCID: PMC1302452, DOI: 10.1016/s0006-3495(02)75377-0.Peer-Reviewed Original ResearchConceptsSummation theoremYeast glycolytic oscillationsLimit cycle oscillationsDynamic systemsControl coefficientsBiochemical networksCycle oscillationsOscillatory propertiesControl analysisMetabolic control analysisTheoremGlycolytic oscillationsTime domainOscillationsModel outputDiscrete Fourier transformFrequency domainSteady stateData setsQualitative way
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 pathwayPhosphataseKinasePhosphorylationOccurrence of paradoxical or sustained control by an enzyme when overexpressed: necessary conditions and experimental evidence with regard to hepatic glucokinase
DE ATAURI P, ACERENZA L, KHOLODENKO B, DE LA IGLESIA N, GUINOVART J, AGIUS L, CASCANTE M. Occurrence of paradoxical or sustained control by an enzyme when overexpressed: necessary conditions and experimental evidence with regard to hepatic glucokinase. Biochemical Journal 2001, 355: 787-793. PMID: 11311143, PMCID: PMC1221796, DOI: 10.1042/bj3550787.Peer-Reviewed Original ResearchConceptsRegulatory proteinsFlux control coefficientsParadoxical controlHigh flux control coefficientAllosteric enzymePathway fluxHepatic glucokinaseEnzymeEnzyme activitySigmoidal kineticsEnzyme kineticsControl coefficientsProteinEnzyme increasesGlucokinaseHill coefficientSubstrate concentrationEnzyme concentrationKinetic modeling of energy metabolism and generation of active forms of oxygen in hepatocyte mitochondria.
Demin O, Gorianin I, Kholodenko B, Westerhoff H. Kinetic modeling of energy metabolism and generation of active forms of oxygen in hepatocyte mitochondria. Молекулярная Биология 2001, 35: 1095-104. PMID: 11771135.Peer-Reviewed Original Research
2000
Kinetics and control of oxidative phosphorylation in rat liver mitochondria after chronic ethanol feeding.
Marcinkeviciute A, Mildaziene V, Crumm S, Demin O, Hoek J, Kholodenko B. Kinetics and control of oxidative phosphorylation in rat liver mitochondria after chronic ethanol feeding. Biochemical Journal 2000, 349: 519-26. PMID: 10880351, PMCID: PMC1221175, DOI: 10.1042/0264-6021:3490519.Peer-Reviewed Original ResearchConceptsOxidative phosphorylationRespiratory fluxMitochondrial proton leakRat liver mitochondriaMitochondrial oxidative phosphorylationCytochrome c oxidaseMitochondrial energy metabolismATP synthaseLiver mitochondriaProton leakC oxidaseProtonmotive forceState 3Blocks of reactionsPhosphorylationEnergy metabolismMitochondriaMitochondrial malfunctioningRespiration rateRespiratory activityRespiratory subsystemIndividual functional unitsFunctional unitsWhy 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 concentrationsComplexesCellular information transfer regarded from a stoichiometry and control analysis perspective
Schuster S, Kholodenko B, Westerhoff H. Cellular information transfer regarded from a stoichiometry and control analysis perspective. Biosystems 2000, 55: 73-81. PMID: 10745111, DOI: 10.1016/s0303-2647(99)00085-4.Peer-Reviewed Original Research
1999
Quantification of Short Term Signaling by the Epidermal Growth Factor Receptor*
Kholodenko B, Demin O, Moehren G, Hoek J. Quantification of Short Term Signaling by the Epidermal Growth Factor Receptor*. Journal Of Biological Chemistry 1999, 274: 30169-30181. PMID: 10514507, DOI: 10.1074/jbc.274.42.30169.Peer-Reviewed Original Research
1998
Implications of macromolecular crowding for signal transduction and metabolite channeling
Rohwer J, Postma P, Kholodenko B, Westerhoff H. Implications of macromolecular crowding for signal transduction and metabolite channeling. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 10547-10552. PMID: 9724740, PMCID: PMC27931, DOI: 10.1073/pnas.95.18.10547.Peer-Reviewed Original ResearchConceptsPhosphotransferase systemMacromolecular crowdingFlux response coefficientsCarbohydrate phosphotransferase systemGlucose phosphotransferase systemBacterial phosphoenolpyruvateSignal transductionMetabolite channelingCell-free extractsProtein concentrationEnzyme complexCarbohydrate phosphorylationPEG 6000 concentrationPolyethylene glycol 6000Total enzyme concentrationHigh protein concentrationsEscherichia coliLow protein concentrationsForm complexesGroup-transfer pathwaysMetabolic behaviorPEG 6000Crowded environmentsMetabolic 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 ResearchSubtleties in control by metabolic channelling and enzyme organization
Kholodenko B, Rohwer J, Cascante M, Westerhoff H. Subtleties in control by metabolic channelling and enzyme organization. Molecular And Cellular Biochemistry 1998, 184: 311-320. PMID: 9746327, DOI: 10.1023/a:1006809028612.Peer-Reviewed Original ResearchConceptsPhosphotransferase systemMetabolic control analysisBacterial phosphotransferase systemEnzyme-enzyme associationsDirect metabolite transferEnzyme organizationConcomitant phosphorylationTernary complex formationPTS pathwayMetabolite transferEnzyme sequestrationMetabolic channellingLiving cellsMacromolecular crowdingPhosphoryl groupEnzyme controlTernary complexCell functionPathwayEnzymeComplex formationIdeal systemEnzyme control coefficientsMetabolic systemsControl coefficientsA model of O·2- generation in the complex III of the electron transport chain
Demin O, Kholodenko B, Skulachev V. A model of O·2- generation in the complex III of the electron transport chain. Molecular And Cellular Biochemistry 1998, 184: 21-33. PMID: 9746310, DOI: 10.1023/a:1006849920918.Peer-Reviewed Original ResearchControl analysis of metabolic systems involving quasi-equilibrium reactions
Kholodenko B, Schuster S, Garcia J, Westerhoff H, Cascante M. Control analysis of metabolic systems involving quasi-equilibrium reactions. Biochimica Et Biophysica Acta 1998, 1379: 337-352. PMID: 9545597, DOI: 10.1016/s0304-4165(97)00114-1.Peer-Reviewed Original Research
1997
Quantification of information transfer via cellular signal transduction pathways
Kholodenko B, Hoek J, Westerhoff H, Brown G. Quantification of information transfer via cellular signal transduction pathways. FEBS Letters 1997, 414: 430-434. PMID: 9315734, DOI: 10.1016/s0014-5793(97)01018-1.Peer-Reviewed Original Research
1996
Ca2+ stimulates both the respiratory and phosphorylation subsystems in rat heart mitochondria
MILDAZIENE V, BANIENE R, NAUCIENE Z, MARCINKEVICIUTE A, MORKUNIENE R, BORUTAITE V, KHOLODENKO B, BROWN G. Ca2+ stimulates both the respiratory and phosphorylation subsystems in rat heart mitochondria. Biochemical Journal 1996, 320: 329-334. PMID: 8947505, PMCID: PMC1217935, DOI: 10.1042/bj3200329.Peer-Reviewed Original ResearchConceptsPhosphorylation systemPhosphorylation subsystemProton leakRat heart mitochondriaMitochondrial membrane potentialHeart mitochondriaIsolated rat heart mitochondriaOxidative phosphorylationRespiratory chainMitochondrial respirationStimulation of respirationSuccinate oxidationMembrane potentialPhosphorylationMitochondriaRespiration rateRespirationPhysiological concentrationsRespiratory subsystemState 3Ca2Free Ca2Strong control on the transit time in metabolic channelling
Kholodenko B, Sakamoto N, Puigjaner J, Westerhoff H, Cascante M. Strong control on the transit time in metabolic channelling. FEBS Letters 1996, 389: 123-125. PMID: 8766813, DOI: 10.1016/0014-5793(96)00532-7.Peer-Reviewed Original Research