Featured Publications
Scaffolding Protein Grb2-associated Binder 1 Sustains Epidermal Growth Factor-induced Mitogenic and Survival Signaling by Multiple Positive Feedback Loops*
Kiyatkin A, Aksamitiene E, Markevich NI, Borisov NM, Hoek JB, Kholodenko BN. Scaffolding Protein Grb2-associated Binder 1 Sustains Epidermal Growth Factor-induced Mitogenic and Survival Signaling by Multiple Positive Feedback Loops*. Journal Of Biological Chemistry 2006, 281: 19925-19938. PMID: 16687399, PMCID: PMC2312093, DOI: 10.1074/jbc.m600482200.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingCarcinoma, Squamous CellCell DivisionCell LineCell Line, TumorCell SurvivalEpidermal Growth FactorFeedbackGuanosine DiphosphateGuanosine TriphosphateHumansModels, BiologicalTransfectionConceptsEpidermal growth factorRas/MAPK signalingGab1 tyrosine phosphorylationGrowth factorRole of Gab1PI3K/Akt activationMultiple positive feedback loopsProtein Grb2Mutant proteinsScaffold proteinTyrosine phosphorylationBinder 1Positive feedback loopMitogenic pathwaysMAPK signalingEssential functionsSurvival signalingDiverse perturbationsCellular responsesAkt activationCytokine receptorsPharmacological inhibitorsGab1EGF dosesGrb2
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
Systems‐level interactions between insulin–EGF networks amplify mitogenic signaling
Borisov N, Aksamitiene E, Kiyatkin A, Legewie S, Berkhout J, Maiwald T, Kaimachnikov NP, Timmer J, Hoek JB, Kholodenko BN. Systems‐level interactions between insulin–EGF networks amplify mitogenic signaling. Molecular Systems Biology 2009, 5: msb200919. PMID: 19357636, PMCID: PMC2683723, DOI: 10.1038/msb.2009.19.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingCell LineDose-Response Relationship, DrugDrug SynergismEnzyme ActivationEpidermal Growth FactorGRB2 Adaptor ProteinHumansImmunoprecipitationInsulinMitogen-Activated Protein KinasesMitogensModels, BiologicalPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Kinase InhibitorsProtein Tyrosine Phosphatase, Non-Receptor Type 11Ras ProteinsReproducibility of ResultsSignal TransductionSrc-Family KinasesSystems BiologyConceptsInsulin receptor substrateEpidermal growth factorRas/ERK cascadeCrosstalk mechanismsComplex cellular responsesPhosphatase SHP2Mitogenic signalingERK cascadeSrc kinaseReceptor substrateERK activityRaf levelsInsulin-induced increaseERK activationCellular responsesGab1HEK293 cellsExternal cuesEGF dosesPoor activatorGrowth factorMitogenicMitogenic responseComputational approachSHP2