Nox1 activation by βPix and the role of Ser‐340 phosphorylation

摘要

RacisanactivatingfactorforNox1,anO2?‐generatingNADPHoxidase,expressedinthecolonandothertissues.RacrequiresaGDP‐GTPexchangefactorforactivation.Nox1activationbyβPixhasbeendemonstratedincelllines.WeexaminedtheeffectsofβPixanditsphosphomimeticmutantonendogenousNox1inCaco‐2cellstransfectedwithNoxo1andNoxa1.βPixexpressionenhancedO2?productioninrestingcellsandcellsstimulatedwithEGForphorbolester.βPix(S340E)furtherenhancedO2?production,whileβPix(S340A)eliminatedtheβPixeffect.βPix(S340E),butnotβPix(S340A),hadhigheraffinityandGEFactivityforRacthanwild‐typeβPix.TheseresultssuggestthatβPixphosphorylationatSer‐340upregulatesNox1throughRacactivation,confirmingRacasatriggerforacuteNox1‐dependentROSproduction...