Drug Resistance Resulting from Kinase Dimerization Is Rationalized by Thermodynamic Factors Describing Allosteric Inhibitor Effects
Kholodenko BN. Drug Resistance Resulting from Kinase Dimerization Is Rationalized by Thermodynamic Factors Describing Allosteric Inhibitor Effects. Cell Reports 2015, 12: 1939-1949. PMID: 26344764, DOI: 10.1016/j.celrep.2015.08.014.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationCell Line, TumorDrug Resistance, NeoplasmHumansMutationPhosphorylationProtein Kinase InhibitorsProtein MultimerizationProto-Oncogene Proteins B-rafThermodynamicsMitogen-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