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PKCcatalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase
Thephosphorylationofmyosinaffectsitsroleinsmoothmusclecontraction,plateletformationandpossIBLyotherprocesses.Phosphorylationbymyosinlightchainkinase(MLCK)increasesmyosinactivityanddephosphorylationbymyosinphosphatasedecreasesmyosinactivity.CPI,afactorthatbindstoandinhibitsmyosinphosphatase,isatargetofphosphorylationbyPKCandPKN.TheinhibitoryactivityofCPIisregulatedbyitsownphosphorylationstate;whenCPIisphosphorylated,itsinhibitoryactivityisincreased.TheactivationofsignaltransductioncascadessuchasGPCRpathwayscanleadtoactivationofPKC,phosphorylationofCPI,inhibitionofmyosinphosphatase,increasedmyosinphosphorylationandincreasedsmoothmusclecontractionorplateletrelease.Theactionofhistamineinvasoconstriction,forexample,maybemediatedbyactivationofPKCthroughthehistaminereceptor,resultinginphosphorylationofCPI-17,increasedinhibitionofmyosinphosphatase,andincreasedsmoothmusclecontraction.
Contributor:GlennCroston,PhD
REFERENCES:HamaguchiT,etal.(2000)Biochem.Biophys.Res.Commun.274(3):825-30.PhosphorylationofCPI-17,aninhibitorofmyosinphosphatase,byproteinkinaseN.KitazawaT,etal.(2000)J.Biol.Chem.;275(14):9897-900.AgoNISTstriggerGprotein-mediatedactivationoftheCPI-17inhibitorphosphoproteinofmyosinlightchainphosphatasetoenhancevascularsmoothmusclecontractility.WatanabeYetal.(2001)Blood97(12):3798-805.ProteinkinaseC-catalyzedphosphorylationofaninhibitoryphosphoproteinofmyosinphosphataseisinvolvedinhumanplateletsecretion.
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