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1、Apoptosis2003;8:19–27C2003KluwerAcademicPublishersRegulationofcellapoptosisbyproteinkinasecδC.BrodieandP.M.BlumbergGonda(Goldschmied)MedicalDiagnosisResearchCenter,FacultyofLife-Sciences,Bar-IlanUniversity,Ramat-Gan52900,Israel(C.Brodie);LaboratoryofCellularCarcin
2、ogenesisandTumorPromotion,NCI,NationalInstitutesofHealth,Bethesda,Maryland20892,USA(P.M.Blumberg)TheisoformsofthePKCfamilyareactivatedinresponseactivatescaspase9,9leadingeventuallytotheactivationoftomitogenicstimuli,toinflammatorystimuli,andtodownstreamcaspases.Both
3、pathwaysresultinthecleav-stressandplayimportantrolesinavarietyofcellularageofcellproteinsandtosubsequentDNAfragmentationfunctionsincludingapoptosis.PKCδamemberoftheandcelldeath.10,11novelPKCsubfamily,isactivelyinvolvedincellapop-tosisinastimulusandtissuespecificmann
4、er;itbothApoptosisisamulti-stageprocess.Proteinkinasespar-regulatestheexpressionandfunctionofapoptoticre-ticipateintheregulationofearlystagesofapoptosisbylatedproteinsandisitselfatargetforcaspases.Activa-phosphorylatingkeyapoptoticproteinsorinlatereventstionofPKCδb
5、yvariousapoptoticstimuliresultsinthe12,13byactingdownstreamofcaspases.Indeed,boththetranslocationofPKCδtodistinctcellularcompartmentssuchasmitochondria,golgiandnucleus,andthediffer-receptor-mediatedapoptosisandthemitochondria-entialtranslocationcontributestoitsdiff
6、erenteffects.Independentapoptoticpathwaysareregulatedbyproteinki-addition,phosphorylationofPKCδondistincttyrosinenasessuchasthoseofthephosphoinositide3-kinase/AKTresiduesanditsassociationwithspecificapoptoticre-pathway,14membersoftheMAPkinasesuperfamily,15latedprote
7、inssuchasc-Abl,DNA-PK,p73andlaminBc-Abl16andvariousisoformsofPKC.17,18arepivotaltoitsfunctionincellapoptosis.Recentfind-ingsontheseaspectsofthePKCδcascadesarethemajorTheproteinkinaseCfamilyofserine-threoninekinasesfocusofthisreview.isactivatedbydiversestimuliandpart
8、icipatesincellularprocessessuchasgrowth,differentiation,andapoptosis.19Keywords:apoptosis;c-Abl;caspases;nucleus;phosphory-ThePKCscomprise12isofo
