MAPK信号转导通路对炎症反应的调控

©1994-2009ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(mitogen-activatedproteink2inase,MAPK),,1991Sturgill(extracellular-signalregulatedproteinkinase,ERK),MAPK[1,2]ERK,c-Jun(c-Junamino-terminalkinase,JNK)/267MAPK***,(,510515):(mitogen-activatedproteinkinase,MAPK),ERKJNK/SAPKp38/RKERK5/BMK1MAPKMAPK,MAPK,MAPK,:;;:Q288RegulationofinflammatoryresponsesbyMAPKsignaltransductionpathways*JIANGYong**,GONGXiao-Wei(DeparmentofPathophysiologyandKeyLaboratoryrShockandMicrocirculationofPLA,FirstMilitaryMedicalUniversity,Guangzhou510515)Abstract:Mitogen-activatedproteinkinase(MAPK),whichisoneoftheimportantsignaltransductionsys2temsinorganisms,isinvolvedinmanycellularprocesses,suchascellgrowth,development,division,differentia2tion,deathandcoordinationofcellularfunctions,andetc.FoursubfamiliesofMAPkinases,i.e.ERK,JNK/SAPK,p38/RKandERK5/BMK1,havebeenidentifiedandclonedinmammaliamcells.TheseMAPkinas2esareactivatedbymanyproinflammatorystimuliandplayanimportantroleinthepathogenesisanddevelop2mentofinflammation.InthisarticlerecentadvancesinthestudyofthemechanismsunderlyingactivationofMAPKsininfectionandinflammationandthemolecularbasisofspecificinhibitorsforMAPKsarereviewed,inspecialreferencewiththeperspectivepreventionandtreatmentofinflammationbythesekinases.Keywords:mitogen-activatedproteinkinase;signaltransduction;inflammatoryresponses,Aug.2000,52(4):267271ActaPhysiologicaSinicaReceived1999-11-01Accepted2000-03-30*ThisstudywesupportedbyNationalScienceFundforDistinguishedYoungScholars(No.39925014),GrantdofNationalNaturalScienceFoundationofChina(No.39830400,No.39800074No.39870332),GrantforOutandingYoungInvestigatorofPLA(No.98J003),andGrantofNaturalScienceFoun2dationofGuangdongProvince(No.980207).**Correspondingauthor.Tel:[phone];Fax:[phone];E-mail:[e-mail]©1994-2009ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(stress-activatedproteinknase,SAPK)p38ERK5/BMK1(bigMAPkinase1)MAPK[13]MAPK;MKKK(MAPkinasekinasekinase),MKK(MAPkinasekinase);(threonine,T)(tyrossine,Y)MAPK[13]MAPK,T-X-Y[46],MAPK,MAPK[69]MAPK,,,MAPKMAPK1MAPK1.1ERKERK:ERK1ERK2ERKEGF(epitheliagrowthfactor)NGF(neuronalgrowthfactor)PDGF(platelet-derivedgrowthfactor)[1,2],ERK,ERK[1,2,10]Dziarski,MW264.7,(solublpeptidoglycan,sPGN)ERK1ERK2,JNK,p38;(lipopolysaccharide,LPS),LPSMAPKs[10]ERK1.2JNK,JNKLPS(TNF-)1(IL-1)DNA[1,2]JNK3:JNK1JNK2JNK3,10[1,2]JNKHa-Ras,TNF-IL-1Ha-RasJNKJNK,c-Junc-JunAP-1(activatingprotein1)[1,2,5]c-Jun,AP-1[5,11]1.3p38p38LPS[12]Lee(cytokine-suppressiveanti-inflammatorydrugs,CSAID),-IL-1TNF-[13]MAPK,CSBP1/2(CSAID-bindingprotein1/2)CSAIDCSBPCSBP1/2p38MAPK[13]LPS,,(erythropoietin,EPO)3(IL-3)H2O2[3,6]MAPK,p38,3p38,p38,p38,p38[7,8,14]4p38,MKK3MKK6p38p38,,p38MKK[8].,Hale,LPS,p38,p38;IL-1p38p38[15],,p38p38,RAW264.7,,LISUV,p38[16,17]p38MAPKp38AWF2CHOP10MEF2C(myocyteenhancerfactor2C)[3,18]MAPK,p38,MAPKAPK2/3(MAPKactivatedproteinkinase2/3)PRAK(p38regulated/activatedproteinkinase)[3,9]/,(smallheat-shockprotein)HSP27,,[9]p38,,[3,6]1.4ERK5ERK5/BMK1TNF-H2O2,©1994-2009ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[19,20],p38MAPKBMK1TNF-c-jun,p38BMK1TNF-c-junp38BMK1MEF2MEF2DTNF-p38BMK1,MEF2AMEF2D,MET2A/MEF2D,TNF-c-jun[20]2MAPKLPS[3,6]LPSERKJNKp38,,,TNFIL-1IL-6IL-8TNF-IL-1(arachdonicacid,AA)MAPK,2.1TMF-TNF-[17]LPS/TNF-,(platelet-activatedfactor,PAF)PAFTNF-IL-1,TNF-IL-1PAF,,LPSRAW264.3p38,;p38LPSTNF-[16,17]ERKJNKp38TNF-,TNF-[20]2.2IL-1IL-1,TNF-IL-6IL-8PMPGsTB()Guan,IL-1p38PGE2NO[21]2.3AAAA(PGs)(LTs)ERK1/22(cyclooxygenase2,COX2),[22]COXPG,PG,p38JNKIL-1COX,PGE2,p38SC68376[23]2.4MAPK,E-(E-selectin)JNKp38E-E-[24]2.5MAPKBruder,ERKIL-8[25].3MAPK,,,[3]MPAK,/[1,3,5]p38MAPK,(two-hybridsystem)p38(myocyte-enhancerfactor2,MEF2)MET2C[18]LPS,p38JNKp38MET2C;c-jun,c-Jun;MAPK?JNKc-Junc-junMEF2Cc-JunAP1,c-JunAP1,[18]MAPK,MAPK,,MAPK(1)4MAPK4.1MAPKp38,SK&F86002SB206718SB220025SB202190SB203580[13,26],[27],p38,,p38SB2021904:MAPK269©1994-2009ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[8,14]p38p38,p38Xp38ATPT106,M109p38[28]p38ATP,ERK,PD98059MEK1/2,ERKPD98059CD3/PMACD3/CD28TTNF-IL-3GM-CSFIFN-IL-6IL-1,IL-4IL-5IL-3[29]JNK4.2MAPKMAPK,Guan,p38SC68376,IL-15p38,NO[21],SB203580[30];SB220025,MAPK,,,,[3,6][1]JiansY(),LiuAH(),ZhaoKS().Thesignaltransductionpathwaysofmitogen-activatedproteinki2nase.JFirstMilMedUniv()1999,19(1):5962(inChinese).[2]ZhangL(),JiansY(),ZhangL()etal.Progressofstudyonmitogen-activatedproteinkinase.ForeignMedSci:sectionPathophysiolClinMed(:),1999,19(2):8487(inChi2nese).[3]JiansY(),HanJH().P38MAPKsignaltrans2ductionpathway.ChinBullLifeSci(),1999,11(3):102106(inChinese).[4]ZhangL(),ZhangL(),JiangY()etal.Theroleofmitogen-activatedproteinKinasesincellapopto2sis.ChemLife(),1998,18(4):1618,(inChinese).[5]JiangY().Progressofstudyonthemechanismofacti2vationofendothelialcellsinducedbylipopolysaccharide.NatlMedJChina(),1999,79(1):7678(inChinese).[6]JiangY(),UlevitchRJ.Thesignaltransductionofcellact