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
2012
Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise
Birtwistle MR, Rauch J, Kiyatkin A, Aksamitiene E, Dobrzyński M, Hoek JB, Kolch W, Ogunnaike BA, Kholodenko BN. Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise. BMC Systems Biology 2012, 6: 109. PMID: 22920937, PMCID: PMC3484110, DOI: 10.1186/1752-0509-6-109.Peer-Reviewed Original ResearchConceptsProtein expression noiseSingle-cell signalingExtracellular signal-regulated kinaseExpression noiseCell variabilityEpidermal growth factor stimulationProtein abundance variationCell fate decisionsPopulation responsesGrowth factor stimulationSingle cellsSignal-regulated kinaseCell population levelProtein expressionSingle-cell levelERK pathway activationFate decisionsPopulation levelFactor stimulationCell signalingCell population responseERK responseBiological outcomesPathway activationCell level
2004
Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades
Markevich N, Hoek J, Kholodenko B. Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades. Journal Of Cell Biology 2004, 164: 353-359. PMID: 14744999, PMCID: PMC2172246, DOI: 10.1083/jcb.200308060.Peer-Reviewed Original ResearchConceptsExtracellular signal-regulated kinaseMultisite phosphorylationProtein kinase cascadeBistable switchSignal-regulated kinaseKinase cascadeMAPK cascadeWidespread mechanismDifferent kinasesSame phosphataseProtein kinasePositive feedback loopProtein activityDephosphorylation reactionsCovalent modificationKinaseMAPK phosphorylationFeedback regulationPhosphorylationKinetic propertiesPhosphataseFeedback loopCascade