HindawiPublishingCorporationJournalofSignalTransduction

Volume2011,ArticleID792639,6pagesdoi:10.1155/2011/792639

ReviewArticle

Mitogen-ActivatedProteinKinasesandReactiveOxygenSpecies:HowCanROSActivateMAPKPathways?

YongSon,1Yong-KwanCheong,1Nam-HoKim,2Hun-TaegChung,3DaeGillKang,4andHyun-OckPae5

1Department2Department

ofAnesthesiologyandPainMedicine,WonkwangUniversitySchoolofMedicine,Iksan570-749,RepublicofKoreaofCardiovascularMedicine,WonkwangUniversityHospital,Iksan570-711,RepublicofKorea

3DepartmentofBiologicalScience,UniversityofUlsan,Ulsan680-749,RepublicofKorea

…… 此处隐藏0字 ……

4ProfessionalGraduateSchoolofOrientalMedicineandHanbangBody-FluidResearchCenter,WonkwangUniversity,Iksan570-749,RepublicofKorea

5DepartmentofMicrobiologyandImmunology,WonkwangUniversitySchoolofMedicine,344-2Shinyong-dong,Iksan,Chonbuk570-749,RepublicofKorea

CorrespondenceshouldbeaddressedtoHyun-OckPae,hopae@wku.ac.krReceived16August2010;Revised25December2010;Accepted11January2011AcademicEditor:ZhilinQu

Copyright©2011YongSonetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.Mitogen-activatedproteinkinases(MAPKs)areserine-threonineproteinkinasesthatplaythemajorroleinsignaltransductionfromthecellsurfacetothenucleus.MAPKs,whichconsistofgrowthfactor-regulatedextracellularsignal-relatedkinases(ERKs),andthestress-activatedMAPKs,c-junNH2-terminalkinases(JNKs)andp38MAPKs,arepartofathree-kinasesignalingmodulecomposedoftheMAPK,anMAPKkinase(MAP2K)andanMAPKkinase(MAP3K).MAP3KsphosphorylateMAP2Ks,whichinturnactivateMAPKs.MAPKphosphatases(MKPs),whichrecognizetheTXYaminoacidmotifpresentinMAPKs,dephosphorylateanddeactivateMAPKs.MAPKpathwaysareknowntobein uencednotonlybyreceptorligandinteractions,butalsobydi erentstressorsplacedonthecell.OnetypeofstressthatinducespotentialactivationofMAPKpathwaysistheoxidativestresscausedbyreactiveoxygenspecies(ROS).Generally,increasedROSproductioninacellleadstotheactivationofERKs,JNKs,orp38MAPKs,butthemechanismsbywhichROScanactivatethesekinasesareunclear.Oxidativemodi cationsofMAPKsignalingproteinsandinactivationand/ordegradationofMKPsmayprovidetheplausiblemechanismsforactivationofMAPKpathwaysbyROS,whichwillbereviewedinthispaper.

1.Introduction

Mitogen-activatedproteinkinases(MAPKs)composeafamilyofproteinkinasesthatplayanessentialroleinrelayingextracellularsignalsfromthecellmembranetothenucleusviaacascadeofphosphorylationeventsandarenegativelyregulatedbyMAPKphosphatases(MKPs)[1].Diversecellularfunctions,rangingfromcellsurvivaltocelldeath,areregulatedbyMAPKsignaling[2].AnumberofextracellularandintracellularstimulihavebeenshowntoactivateMAPKpathwaysatcellularlevels[3],implyingthattheremaybetightandspeci cregulationofMAPKactivationbyacertainstimulus.Interestingly,reactiveoxygen

species(ROS)canactivateMAPKpathways[4],butthemechanism(s)forthise ectisunclear.

BesidesMAPKs,othersignalingmolecules(e.g.,pro-teintyrosinephosphatases,proteintyrosinekinases,andtranscriptionalfactors)canalsobeactivatedbyROS[5],suggestingthatROSmayhavemeaningfulrolesasregulatorsofcellfunctionorassignalingmolecules.Indeed,mountingevidencesupportsaphysiologicalroleforROSasa“secondmessenger”inintracellularsignalingcascadesthatcontrolcellgrowth,proliferation,migration,andapoptosis[5].BecausetheMAPKpathwaysmediatebothmitogen-andstress-activatedsignals,therehasbeensigni cantinterestintheregulationofthesepathwaysbyROS.Thispaperwill