2020
Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D
Kennedy S, Jarboui M, Srihari S, Raso C, Bryan K, Dernayka L, Charitou T, Bernal-Llinares M, Herrera-Montavez C, Krstic A, Matallanas D, Kotlyar M, Jurisica I, Curak J, Wong V, Stagljar I, LeBihan T, Imrie L, Pillai P, Lynn M, Fasterius E, Al-Khalili Szigyarto C, Breen J, Kiel C, Serrano L, Rauch N, Rukhlenko O, Kholodenko B, Iglesias-Martinez L, Ryan C, Pilkington R, Cammareri P, Sansom O, Shave S, Auer M, Horn N, Klose F, Ueffing M, Boldt K, Lynn D, Kolch W. Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D. Nature Communications 2020, 11: 499. PMID: 31980649, PMCID: PMC6981206, DOI: 10.1038/s41467-019-14224-9.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptor (EGFR) networkGrowth factor receptor networkFundamental biological processesColorectal cancer cellsCancer cellsEGFR networkTranscriptional regulationProtein complexesExtensive rewiringCellular phenotypesInteraction networksBiological processesOncogenic mutationsOncogenic KRAS mutationsReceptor networkGenetic alterationsProtein expressionPPInsMutationsCellsInteractorsPhosphorylationRewiringPoor patient outcomesSignal flow
2015
Mitogen-Inducible Gene-6 Mediates Feedback Inhibition from Mutated BRAF towards the Epidermal Growth Factor Receptor and Thereby Limits Malignant Transformation
Milewska M, Romano D, Herrero A, Guerriero ML, Birtwistle M, Quehenberger F, Hatzl S, Kholodenko BN, Segatto O, Kolch W, Zebisch A. Mitogen-Inducible Gene-6 Mediates Feedback Inhibition from Mutated BRAF towards the Epidermal Growth Factor Receptor and Thereby Limits Malignant Transformation. PLOS ONE 2015, 10: e0129859. PMID: 26065894, PMCID: PMC4466796, DOI: 10.1371/journal.pone.0129859.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAdaptor Proteins, Signal TransducingAdultAnimalsCell Transformation, NeoplasticChlorocebus aethiopsCOS CellsErbB ReceptorsFeedback, PhysiologicalGene Expression Regulation, NeoplasticHEK293 CellsHumansMiceMiddle AgedMutation, MissenseProto-Oncogene Proteins B-rafThyroid NeoplasmsTumor Suppressor ProteinsConceptsMitogen-inducible gene 6Epidermal growth factor receptorOncogenic BRAFGrowth factor receptorGene 6Mig-6 expressionRAS-ERK pathwayRAS-ERK signalingFactor receptorNegative regulatory loopSignal-regulated kinaseInducible gene 6Focus formation assayBRAF kinase activityGenetic interactionsPI3K/AktCellular transformationTranscriptional levelBRAF functionCell line modelsKinase activityEGFR activationMethylation dataRegulatory loopNegative feedback circuit
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
2002
Modular Response Analysis of Cellular Regulatory Networks
BRUGGEMAN F, WESTERHOFF H, HOEK J, KHOLODENKO B. Modular Response Analysis of Cellular Regulatory Networks. Journal Of Theoretical Biology 2002, 218: 507-520. PMID: 12384053, DOI: 10.1006/jtbi.2002.3096.Peer-Reviewed Original ResearchConceptsRegulatory networksMitogen-activated protein kinase cascadeEpidermal growth factor receptor (EGFR) networkGrowth factor receptor networkProtein kinase cascadeIntermodular interactionsCellular regulatory networksModular Response AnalysisIntracellular regulatory networksAmmonium assimilationKinase cascadeMolecular biological analysisGenetic circuitsInteraction mapSignal transducingEscherichia coliReceptor networkModular organizationMolecular interactionsBiological analysisSignal transferColiTransducingRegulationInteraction
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 pathwayPhosphataseKinasePhosphorylation
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