ThedefectsincAMP-regulatedchloridechannelCTFRarebelievedtobethemajorcauseforcysticfibrosis.RegulationofCFTRproteinbythesurfacereceptorbetaadrenergicreceptorismediatedthroughtheezrin/rADIxin/moesinbindingphosphoprotein50(EBP50),whichbindsboththeC-terminiCFTRandb2ARthroughtheirPDZbindingmotifs.Intherestingstate,CFTR,b2AR,andEBP50existasamacromolecularcomplexontheapicalsurfaceofepithelialcells.UponagoNISTactivationoftheb2AR,theadenulatecyclaseisstimulatedthroughtheGproteinpathway,leadingtoanincreaseincAMP.TheelevatedconcentrationofcAMPactivatesPKA,whichisanchorednearCFTRviainteractionwithEzrin.ThephosphorylationofCFTRbyPKAdisruptsthecomplexandleadstocompartmentalizedandspecificsignalingofthechannel.

Contributor:RogerAnderson,PhD

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