2015
G Protein–Coupled Receptor Signaling Networks from a Systems Perspective
Roth S, Kholodenko B, Smit M, Bruggeman F. G Protein–Coupled Receptor Signaling Networks from a Systems Perspective. Molecular Pharmacology 2015, 88: 604-616. PMID: 26162865, DOI: 10.1124/mol.115.100057.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsRole of GPCRsSignal transduction networksProtein-protein interactionsSystems biology studiesSystems biology researchProtein-coupled receptorsCell surface receptorsSignaling networksExtracellular signalsMammalian cellsSignaling routeSingle proteinIntracellular proteinsExternal cuesAdaptive responseBiophysical conceptsProteinReceptorsFeedforward circuitryCellsConformationResponseCues
2008
Domain-oriented reduction of rule-based network models.
Borisov N, Chistopolsky A, Faeder J, Kholodenko B. Domain-oriented reduction of rule-based network models. IET Systems Biology 2008, 2: 342-51. PMID: 19045829, PMCID: PMC2628550, DOI: 10.1049/iet-syb:20070081.Peer-Reviewed Original ResearchConceptsMulti-domain proteinsAuxiliary proteinsMembrane-bound receptorsTranscriptional regulatorsProgenitor proteinsProtein interactionsComplex assemblyGrowth factor receptorProteinFactor receptorSpeciesCorrect mass balanceEffector functionsHeterodimerisationReceptorsSitesRegulatorAssemblyInteractionDomain
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
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