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