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 monophosphateERKAltered store operated calcium entry increases cyclic 3′,5′‐adenosine monophosphate production and extracellular signal‐regulated kinases 1 and 2 phosphorylation in polycystin‐2‐defective cholangiocytes
Spirli C, Locatelli L, Fiorotto R, Morell CM, Fabris L, Pozzan T, Strazzabosco M. Altered store operated calcium entry increases cyclic 3′,5′‐adenosine monophosphate production and extracellular signal‐regulated kinases 1 and 2 phosphorylation in polycystin‐2‐defective cholangiocytes. Hepatology 2012, 55: 856-868. PMID: 21987453, PMCID: PMC3272110, DOI: 10.1002/hep.24723.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl CyclasesAnimalsBile DuctsCalciumCalcium ChannelsCalcium SignalingCells, CulturedCyclic AMPCyclic AMP-Dependent Protein KinasesHomeostasisMembrane GlycoproteinsMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Models, AnimalPhosphorylationSignal TransductionStromal Interaction Molecule 1TRPP Cation ChannelsVascular Endothelial Growth Factor AConceptsSensor stromal interaction molecule 1Adenylyl cyclase type 6Extracellular signal-regulated kinases 1Signal-regulated kinases 1Overproduction of cAMPStromal interaction molecule 1Orai channelsWild-type miceSOCE activationCAMP productionRapamycin (mTOR) signalingKinase 1ERK pathwayERK1/2 activationHuman diseasesWT cellsMammalian targetDependent activationSTIM-1CAMP/Inappropriate activationCyst growthCystic cholangiocytesPolycystic liver diseaseActivation