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5-8.Anti-AKAP150Antibody,preincubatedwiththecontrolpeptideantigen.
- Schwartz,J.H.(2001)Proc.Natl.Acad.Sci.USA.98,13482.
- Feliciello,A.etal.(2001)J.Mol.Biol.308,99.
- Adler,E.M.(2014)J.Gen.Physiol.143,313.
- Esseltine,J.L.andScott,J.D.(2013)Trends.Pharmacol.Sci.34,648.
- Ting,J.T.etal.(2012)Annu.Rev.Neurosci.35,49.
- Nieves-Cintron,M.etal.(2015)Cell.Signal.Onlinepublication.
A-Kinaseanchorproteins(AKAPs)areagroupofstructurallydiverseproteinsthatbindtotheregulatoryunitofProteinKinaseA(PKA)todiscretelocationswithinthecell1.AKAPsincludetwoconservedstructuralmodules:AtargetingdomainthatservesasascaffoldandmembraneanchorthatconsistsoftwoNH2-terminalstructuralmodulesthatarehighlyconservedamongmammalianhomologues.TheyalsohaveatetheringdomainthatinteractswithPKAregulatorysubunitswhichconsistsofashortamphipathichelix.AlternativesplicingcanshuffletargetingandtetheringdomainstogenerateavarietyofAKAPswithdifferenttargetingspecificity.AlthoughAKAPshavebeenidentifiedonthebasisoftheirinteractionwithPKA,theyalsobindothersignalingmolecules,mainlyphosphatasesandkinasesthatregulateAKAPtargetingandactivateothersignaltransductionpathways2.
SometypesofAKAPsinteractwith CaV1.1 and CaV1.2.ThesevoltagegatedcalciumchannelsarephosphorylatedbyPKAafterβ-adrenergicactivation.ThisphosphorylationisenabledbythebindingofAKAP150tothedistalC-terminalofCaV1.1andCaV1.2.BindingofdifferentAKAPsthatinteractwithdistinctsignalingpartnerstothecalciumchannelintracellularC-terminaldomainmayacttofine-tunechannelactivityanddownstreamcalcium-mediatedprocesses3.
AsinglesubtypeofneuronalAKAPisexpressedwidelyinthebrainandishighlyconservedinmouse(150kDA),bovine(75kDA)andhuman(79kDA).APAK150targetsPKAIItothepostsynapticCytoskeletonandperikaryaofneurons.ItisexpressedinPurkinjecellsandinolfactorybulbneurons,basalganglia,cerebralcortexandotherforebrainareas.AKAP150isconcentratedinprimarybranchesofdendritesinassociationwithmicrotubules.ThelocalizationofPKAIIβinbrainoverlapswiththatofAKAP150,suggestingthatAKAP150istherelevantPKAIIβanchorproteininthebrain2.
InhibitionofeitherAKAP150or TRPV1 bindingsitescausesanabolishmentofPKC-dependentTRPV1sensitizationtocapsaicinstimulithusmakingtheAKAP150-TRPV1interactionaviabletargetfornovelanalgesics4.
AKAP150interactswithanothergroupofscaffoldingproteinsknownastheSAP90/PSD95-associatedproteinfamily.AKAP150interactsdirectlywiththeSH3andGKdomainsof PSD95 and SAP97.Theseproteinshavespecificrolesinsynapticlocalizationof NMDARs and AMPARs respectively5.
Postmyocardialinfarction,AKAP150-mediatedtargetingofcalcineurintosarcolemmalmicro-domainsinventricularmyocytescontributestothelocalandacutegeneremodelingeventsthatleadtothedown-regulationof KV currents6.
Anti-AKAP150Antibody(#APZ-031)isahighlyspecificantibodydirectedagainstanepitopeoftheratprotein.Theantibodycanbeusedinwesternblotanalysis.IthasbeendesignedtorecognizeAKAP150frommouseandratsamples.TheantibodywillunlikelyrecognizeAKAP150fromhumansamples.

5-8.Anti-AKAP150Antibody,preincubatedwiththecontrolpeptideantigen.


