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1、AbstraCt中文摘要AbbreviationSListofFiguresListofTablesTableofcontentsChapterIReview:PP2Aanderythropoiesis11PP2Aisaserine/threonjnephosphataseKinasesphosphatasesandPSPsPP2Aholoenzymeholds0comprehensivestructureCellularlocaliz
2、ationandmultistepregulationChemicalinhibitorshumandiseasesandanimalmodels12Hematopoiesisanderythropoiesis—keepinglifegoingonInsightsintohematopoiesis—hotspringfo廠bloodcellsTheb『0logyoferythropoiesiskeepingbloodredReferen
3、cesChapterIhLossofPpp2coalleleinTie2tissuesleadstofetalliveranemiantroductionMaterialsandmethods21EstablishPpp2caconditionalknockoutmice22LossofthePpp2caallelewithinTie2cellsresultsinembryoniclethality23Mutantembryosexhi
4、bitnormalvasculature24PP2Acc£。deficientembryossufferimpaireddefectivehematopoiesis25AdultmutantmicemanifestnormalhematopoieticparametersDiscussionContributions13578910101214161919232912501231354445555666THESIS:Embryonica
5、nemiainPpp2cadeletedmiceSPECIALIZATION:GeneticsPhDCANDIDATE:WeiqianCHENSUPERVISOR:XiangGAO,ProfessorAbstractProteinphosphatase2A(PP2A)isthemostabundantphosphatasespecificforserineandthreoninephosphorylationItiscomposedof
6、acommonheteromericcoreenzyme,thatiscomposedofacatalyticsubunit(C)andascaffoldingsubunit(A),whichassociateswithavarietyofregulatorysubunits(B)Thecatalyticsubunit(PP2Ac)hastwoisoforms:PP2Acoc_(encodedbythePpp2cagene)andPP2
7、Acl3(encodedbythePpp2cbgene)PP2AcocisconsideredasthemainfunctionalPP2Acisoform,becauseofits10foldabundancethanPP2Acl3inmostmousetissuesDephosphoryIationofsubstratestargetedbyPP2Amediatesalargevarietyofbiologicalprocesses
8、IsuchasproliferationIsurvival|differentiationlmigrationandadhesionThevastarchiveofchemicalinhibitors,animalmodelsandrelatedstudiesdemonstratethatPP2Aphosphataseactivityisimportantintumorigenesis,nervedegeneration,hematop
9、oiesis,myocardiumcontractilemaintenance,andenergybalanceHoweverpreciseknowledgeaboutitsfunctionindevelopmentalbiologyespeciallytheestablishmentofthevascularandbloodsystem,needstobeanalyzedindetailInthisstudywedeletedthef
10、loxedPpp2calocusinendothelialandhematopoieticprogenitorcellswithaTie2CretransgeneBriefly40%Tie2Cre/Ppp2cdI/FembryosdiedbetweenEIO5andE145,whereas116%mutantswerebornnormallyUnexpectedlyPP2Ac僅一deficientembryosdidnotmanifes
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