2021
RAF1 amplification drives a subset of bladder tumors and confers sensitivity to MAPK-directed therapeutics
Bekele RT, Samant AS, Nassar AH, So J, Garcia EP, Curran CR, Hwang JH, Mayhew DL, Nag A, Thorner AR, Börcsök J, Sztupinszki Z, Pan CX, Bellmunt J, Kwiatkowski DJ, Sonpavde GP, Van Allen EM, Mouw KW. RAF1 amplification drives a subset of bladder tumors and confers sensitivity to MAPK-directed therapeutics. Journal Of Clinical Investigation 2021, 131 PMID: 34554931, PMCID: PMC8592548, DOI: 10.1172/jci147849.Peer-Reviewed Original ResearchConceptsBladder tumorsUrothelial tumorsTherapeutic strategiesNovel therapeutic strategiesRational therapeutic strategiesPatient-derived modelsRaf/MEK/ERKClinical outcomesMEK/ERKTreatment optionsBladder cancerHeterogeneous diseaseMEK inhibitionTumorsUnique subsetFocal amplificationRAF inhibitorsCell linesRAF1Gene expression patternsActivationExpression patternsSignalingSubsetRaf1 activity
2018
Dissecting RAF Inhibitor Resistance by Structure-based Modeling Reveals Ways to Overcome Oncogenic RAS Signaling
Rukhlenko OS, Khorsand F, Krstic A, Rozanc J, Alexopoulos LG, Rauch N, Erickson KE, Hlavacek WS, Posner RG, Gómez-Coca S, Rosta E, Fitzgibbon C, Matallanas D, Rauch J, Kolch W, Kholodenko BN. Dissecting RAF Inhibitor Resistance by Structure-based Modeling Reveals Ways to Overcome Oncogenic RAS Signaling. Cell Systems 2018, 7: 161-179.e14. PMID: 30007540, PMCID: PMC6149545, DOI: 10.1016/j.cels.2018.06.002.Peer-Reviewed Original ResearchConceptsOncogenic RasERK signalingRas/ERK pathwayRAF inhibitorsOncogenic Ras signalingMEK/ERKStructure-based modelingRAF inhibitor resistanceRAS mutant tumorsRas signalingPosttranslational modificationsRaf kinaseERK activityRAF dimerizationDrug-protein interactionsERK pathwayMultiple inhibitorsColony formationSignalingMutant NRASCell proliferationDrug designParadoxical activationInhibitor resistanceMechanistic dynamic model
2012
Cyclic AMP/PKA‐dependent paradoxical activation of Raf/MEK/ERK signaling in polycystin‐2 defective mice treated with sorafenib
Spirli C, Morell CM, Locatelli L, Okolicsanyi S, Ferrero C, Kim AK, Fabris L, Fiorotto R, Strazzabosco M. Cyclic AMP/PKA‐dependent paradoxical activation of Raf/MEK/ERK signaling in polycystin‐2 defective mice treated with sorafenib. Hepatology 2012, 56: 2363-2374. PMID: 22653837, PMCID: PMC3460040, DOI: 10.1002/hep.25872.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, HormonalBenzenesulfonatesBile DuctsCaspase 3Cell ProliferationCells, CulturedCyclic AMP-Dependent Protein KinasesCystsDrug Therapy, CombinationEpithelial CellsKi-67 AntigenLiver DiseasesMAP Kinase Signaling SystemMiceMice, KnockoutNiacinamideOctreotidePhenylurea CompoundsPhosphorylationProtein Kinase InhibitorsProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-rafPyridinesSorafenibTRPP Cation ChannelsConceptsRaf-1Cell proliferationB-RafPhosphorylated ERKRaf kinase activitySignal-regulated kinase 1/2 pathwayRAF inhibitorsCyclic adenosine monophosphateRaf/MEK/ERKCyst growthDefective miceKinase 1/2 pathwayParadoxical activationCAMP/PKAMEK/ERKPolycystin-2Kinase AKinase activityWT cellsDependent activationERK1/2 phosphorylationInhibitor 14Epithelial cellsAdenosine monophosphateERKBRAF mutation testing in clinical practice
Ziai J, Hui P. BRAF mutation testing in clinical practice. Expert Review Of Molecular Diagnostics 2012, 12: 127-138. PMID: 22369373, DOI: 10.1586/erm.12.1.Peer-Reviewed Original ResearchConceptsHairy cell leukemiaBRAF mutation testingPapillary thyroid carcinomaMalignant melanomaThyroid carcinomaCell leukemiaClinical practiceCutaneous malignant melanomaSerine/threonine-protein kinase BRAFCurrent clinical practiceImportant biological markerMEK/ERKTreatment paradigmClinical trialsHigh prevalenceBRAF inhibitorsBRAF mutationsMutation testingPrecision cancer therapyTherapeutic guidanceMutant BRAFLethal diseaseBiological markersCancerHuman cancers
2005
Serotonin 5-HT1A Receptors Regulate NMDA Receptor Channels through a Microtubule-Dependent Mechanism
Yuen EY, Jiang Q, Chen P, Gu Z, Feng J, Yan Z. Serotonin 5-HT1A Receptors Regulate NMDA Receptor Channels through a Microtubule-Dependent Mechanism. Journal Of Neuroscience 2005, 25: 5488-5501. PMID: 15944377, PMCID: PMC6724987, DOI: 10.1523/jneurosci.1187-05.2005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein KinasesDendritesExtracellular Signal-Regulated MAP KinasesIn Vitro TechniquesKinesinsMembrane PotentialsMicrotubulesMolecular Motor ProteinsNeuronsPatch-Clamp TechniquesPrefrontal CortexProtein SubunitsProtein TransportRatsReceptor, Serotonin, 5-HT1AReceptors, N-Methyl-D-AspartateSerotoninSerotonin 5-HT1 Receptor AgonistsSynapsesConceptsMicrotubule-dependent mechanismMEK/ERKNMDA receptorsPrefrontal cortexMicrotubule stabilityDendritic transportNMDAR interactionMicrotubule assemblyBiochemical evidenceMEK inhibitorsPFC pyramidal neuronsNMDA receptor channelsRole of serotoninCaMKIIERKNeuronal dendritesNMDAR functionMicrotubule stabilizerPathological conditionsPrimary targetReceptor channelsPyramidal neuronsNMDAR currentsSerotonin systemReceptors
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