shp2参与调控il22活化肿瘤细胞mapk通路

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1、扬州大学硕士学位论文结果1．构建质粒pcDNA3．1-IL22R1一flag、pcDNA3．1一IL一22Rl-Y251F-flag、pcDNA3．1-IL一22R1-Y301F—flag、pcDNA3．1一IL一22R1一FF—flag、pcDNA5／FRT-IL22R1-Flag、pcDNA5／FRT—IL22R1一FF—Flag，用于瞬时表达。2．构建稳定表达细胞系Flp-In一293／IL一22R1、Flp—In一293／IL一22R1一FF。．3．IL-22可诱导Shp2与IL-22R1的结合，以及Src

2、，Erkl／2和sTAT3的活化。4．在HEK293中，内外源Shp2都可与瞬时表达的IL．22R1结合。5．IL-22R1的Tyr-251和Tyr-301位点对其与Shp2结合及IL-22束1]激引起Erk2、Stat3活化是必需的。6．Shp2的酪氨酸磷酸酶活性对于IL．22诱导的Erk2活化及细胞增殖是必需的。7．Shp2与IL-22R1的结合对IL一22诱导的细胞增殖具有显著影响。综上所述，本研究发现经IL一22束1]激后，Shp2被招募-至-IL一22R1，且IL一22R1的Tyr251及Tyr301位点

3、对于IL一22诱导的Shp2与IL-22R1的结合，及Erk2t]《J活化均是必需的。此外，Shp2与IL一22R1的相互作用与IL一22诱导的STAT3的活化相关，‘这是有关Shp2参与调节IL一22介导的MAPK通路的首次报道。桂秋：Shp2参与调控IL．22活化肿瘤细胞MAPK通路AssociationofShp2withphosphorylatedIL—-22R1isrequiredforInterleukin-—22-·inducedactivationofMAPkinasesCandidate：GuiQ

4、iuSupervisor：AssociateProf．MengSongshuAbstract：Interleukin。22(IL-22)isamemberofIL一10familyofcytokinesproducedbyactivatedTcellsandisinvolvedinseveraltissueresponses．IL一22signalsthroughaheterodimericreceptorcomposedofIL一22receptor1(IL-22R1)andIL．10R2，andtheintra

5、cellularsignalingpathwaysmediatedbyIL-22receptorarenotcompletelyknown．ThisreportshowsthatIL一22inducesIL一22R1phosphorylation，andSrchomology2-containingprotein—tyrosinephosphatase(Shp2)isrecruitedtothetyrosinephosphorylatedIL-22R1uponIL-22stimulation．Furthermore

6、，Tyr-251andTyr-301ofIL一22R1arerequiredforShp2bindingtotheIL-22R1．Shp2bindingtoIL-22R1andSap2proteintyrosinephosphataseactivityarerequiredforactivationofMAPkinasesandsignaltransducersandactivatorsoftranscription3(Stat3)phosphorylationbyIL-22．Theseresultsreveala

7、criticalroleofShp2inIL．22mediatedsignaltransductionpathways．Keywords：Interleukin-22，IL一22receptor1(IL一22R1)，Shp2，MAPkinase，Star3Methods1．Plasmidconstruction2．Cellcultureandtransfection3．Constructionofstable—expressedFlp—In．293celllines4．Detectionofproteinexpre

8、ssiononcellsurface5．Immunoprecipitationandimmunoblotanalysis6．Cellproliferationassay扬州大学硕士学位论文4—Results1．plasmidspcDNA3．1一IL22R1一flag，pcDNA3．1一IL一22R1一Y251F—flag，pcDNA3．1一IL一22R1-Y