ProteinkinaseAregulatorysubunitRIIalpha(PKA-RIIa)istightlyboundtocentrosomalstructuresduringinterphasethroughinteractionwiththeA-kinaseanchoringproteinAKAP350(alsoknownasAKAP450andCGNAP),MAP2andPericentrin.ThisdiagramillustratesthesethreePKA-RIIbindingcomplexes.ThecyclinB-p34(cdc2)kinase(CDK1)hasbeenshowntophosphorylatePKA-RIIaonT54andthishasbeenproposedtoalterthesubcellularlocalizationofPKA-RIIaattheonsetofmitosis.IthasbeendemonstratedthatPKA-RIIadissociatesandredistributesfromcentrosomesatmitosis.ThefocalpointofthisillustrationistheAKAP350complex.InadditiontobindingPKA-RIIa,AKAP350bindsPKN(Takahashietal1999)andthephosphatasesPP1andPPA2(Takahashietal1999).PKNisaserine/threonineproteinkinase,havingacatalyticdomainhomologoustothePKCfamilyintheC-terminalregionandauniqueregulatoryregionintheN-terminalregion.PKNisactivatedbyasmallGTPaseRhoAandunsaturatedfattyacidssuchasarachidonicacid.Thebindingofbothkinasesandphophatasesbythesamescaffoldproteinprovidesafocalpointwherephysiologicalevents,suchascellcycleprogressionandintracellularmembranetraffic,mayberegulatedbyphosphorylationstateofspecificproteinsubstrates.Thereareatleast4isoformsofAKAP350whichleadtothepossibilitythattheymaybehavedifferentlyatdifferentsubcellularlocations.MAP2isamemberofagroupofproteinsthatprovidemicrotubulestABIlization.MAP2affinityappearstobedependentonPKAphosphorylationofMAP2.PericentrinisalsoanAKAP(DivianiandScott).PericentrinbindsDyneinwhichisalsoregulatedbyPKAleADIngtothepossibilitythatpericentrinpositionsPKAtoregulatedyneinfunction(DivianiandScott).AnotherexampleofAKAP/PKAinteractionisillustratedintheAKAP95roleinmitosisandchromosomedynamics”pathway.

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REFERENCES:CarlsonCR,WitczakO,VossebeinL,LabbeJC,SkalheggBS,KeryerG,HerbergFW,CollasP,TaskenK.CDK1-mediatedphosphorylationoftheRIIalpharegulatorysubunitofPKAworksasamolecularswitchthatpromotesdissociationofRIIalphafromcentrosomesatmitosis.JCellSci.2001Sep;114(Pt18):3243-54.DivianiD,ScottJD.AKAPsignalingcomplexesattheCytoskeleton.JCellSci.2001Apr;114(Pt8):1431-7.

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