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 ResearchMeSH KeywordsAnimalsMAP Kinase Signaling SystemModels, BiologicalModels, TheoreticalProtein BindingProtein KinasesSignal TransductionConceptsGene networksFunctional interactionMitogen-activated protein kinase cascadeProtein kinase cascadeProteomic data setsKinase cascadeCellular signalingLarge genomicsUnidentified elementsMechanistic levelCellular networkingSignalingCell systemGenomicsInteractionInteraction routesCascadeComputer-generated responsesNetwork responseCurrent methodologiesResponse
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
Molecular Dynamics Simulations Reveal that Tyr-317 Phosphorylation Reduces Shc Binding Affinity for Phosphotyrosyl Residues of Epidermal Growth Factor Receptor
Suenaga A, Hatakeyama M, Kiyatkin AB, Radhakrishnan R, Taiji M, Kholodenko BN. Molecular Dynamics Simulations Reveal that Tyr-317 Phosphorylation Reduces Shc Binding Affinity for Phosphotyrosyl Residues of Epidermal Growth Factor Receptor. Biophysical Journal 2009, 96: 2278-2288. PMID: 19289054, PMCID: PMC2717265, DOI: 10.1016/j.bpj.2008.11.018.Peer-Reviewed Original ResearchConceptsSrc homology 2Epidermal growth factor receptorGrowth factor receptorPhospho-tyrosine binding (PTB) domainsLinker regionFull-length ShcPhospho-tyrosine residuesKey conformational changesFactor receptorShc interactionTyr-317Protein ShcTyrosine kinase receptorsPhosphorylated ShcPTB domainRas-mitogenHomology 2Phosphorylation resultsPhosphotyrosyl peptidesProtein kinaseTyrosine phosphorylationBinding domainsSubsequent phosphorylationPhosphotyrosyl residuesShc
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