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
2007
Ligand‐dependent responses of the ErbB signaling network: experimental and modeling analyses
Birtwistle MR, Hatakeyama M, Yumoto N, Ogunnaike BA, Hoek JB, Kholodenko BN. Ligand‐dependent responses of the ErbB signaling network: experimental and modeling analyses. Molecular Systems Biology 2007, 3: msb4100188. PMID: 18004277, PMCID: PMC2132449, DOI: 10.1038/msb4100188.Peer-Reviewed Original ResearchMeSH KeywordsAndrostadienesButadienesCell Line, TumorCell MembraneDimerizationEnzyme ActivationEpidermal Growth FactorExtracellular Signal-Regulated MAP KinasesFeedback, PhysiologicalHumansLigandsModels, BiologicalNeuregulin-1NitrilesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Structure, TertiaryProto-Oncogene Proteins c-aktReceptor Protein-Tyrosine KinasesReproducibility of ResultsSignal TransductionWortmanninConceptsEpidermal growth factorERK activityEGF-induced signalingMultiple human cancersPhosphoinositol-3 kinaseLigand-dependent responsesSustained signalingERK activationDownstream proteinsAkt activationInhibitor U0126Major regulatorHuman cancersErbB receptorsLigand dosesHeregulinErbBKinaseSignalingGrowth factorActivationKey roleU0126AktRegulator