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
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 concentration
2000
Why 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
1994
Control theory of one enzyme
Kholodenko B, Westerhoff H. Control theory of one enzyme. Biochimica Et Biophysica Acta 1994, 1208: 294-305. PMID: 7947961, DOI: 10.1016/0167-4838(94)90116-3.Peer-Reviewed Original ResearchConceptsEnzyme catalytic cycleArbitrary kinetic schemesEnzyme catalyzed reactionsStandard free energy differenceControl of reactionsCatalytic cycleElemental stepsFree energy differenceCatalyzed reactionsFree energy dropForward rate constantElemental transitionsReaction rateEnzyme reactionRate constantsEnergy differenceEnzyme statesKinetic schemeReactionEnzyme cycleSingle enzymeEnzymeStepKineticsConstantsRate limitation within a single enzyme is directly related to enzyme intermediate levels
Kholodenko B, Westerhoff H, Brown G. Rate limitation within a single enzyme is directly related to enzyme intermediate levels. FEBS Letters 1994, 349: 131-134. PMID: 8045290, DOI: 10.1016/0014-5793(94)00617-2.Peer-Reviewed Original ResearchGetting to the inside of cells using metabolic control analysis
Westerhoff H, Hofmeyr J, Kholodenko B. Getting to the inside of cells using metabolic control analysis. Biophysical Chemistry 1994, 50: 273-283. PMID: 8011948, DOI: 10.1016/0301-4622(93)e0095-m.Peer-Reviewed Original Research
1981
Dynamic stability of a metabolic pathway with single-loop feedback.
Dibrov B, Zhabotinskiĭ A, Kholodenko B. Dynamic stability of a metabolic pathway with single-loop feedback. Биофизика 1981, 26: 590-5. PMID: 7284447.Peer-Reviewed Original ResearchDynamic stability and parametric stabilization of steady states of unbranched metabolic pathways.
Dibrov B, Zhabotinskiĭ A, Kholodenko B. Dynamic stability and parametric stabilization of steady states of unbranched metabolic pathways. Биофизика 1981, 26: 790-5. PMID: 7317462.Peer-Reviewed Original Research