激活突变酪氨酸磷酸酶shp-2参与髓系增殖性疾病的机制探讨-mechanism of activated mutant tyrosine phosphatase shp - 2 participating in myeloproliferative diseases.docx

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激活突变酪氨酸磷酸酶shp-2参与髓系增殖性疾病的机制探讨-mechanism of activated mutant tyrosine phosphatase shp - 2 participating in myeloproliferative diseases.docx

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激活突变酪氨酸磷酸酶shp-2参与髓系增殖性疾病的机制探讨-mechanism of activated mutant tyrosine phosphatase shp - 2 participating in myeloproliferative diseases

ofleukocytesintheperipheralbloodwasincreaser（P0.05）,spleenswerebiggerinSHP-2D61G/+thaninWT.SIwasheigherin8-week-oldand16-week-oldSHP-2D61G/+thaninWT.FCMshowedthatMac-1andGr-1oftheperipheralbloodleukocyteswereincreasedin16-week-oldSHP-2D61G/+,Mac-1positivecellratewasincreased,Mac-1andGr-1positivecellratewasalsoincreasedinthebonemarrowcellsofSHP-2D61G/+thanWT，whilesurfacemarkerpositivecellrateoftheerythroidandthelymphocytedidnotchangeobviously.TwogroupsofmicewithmyeloidcellsafterinductionwithIL3,thecolony-formingabilityofbonemarrowcellsincreasedmoreobviously,thephosphorylationlevelofErkandAktinthemastcellswashigherinSHP-2D61G/+thaninWT.ThebindingcapacityofSHP-2D61G/+withGab2improvedobviously.ThesepointoutthatSHP-2D61G/+leadstotheproliferationofMyeloidcells,andgivesrisetoincreasethephosphorylationlevelofErk,ArtandthebindingcapacityofmutantSHP-2withGab2.CONCLUSIONS:TheactivatingmutantSHP-2D61G/+involvedinmousemyeloproli-ferativedisorders,themolecularmechanismmaybeassociatedwithSHP-2D61G/+promotesthebindingabilityofGab2,andfurtherparticipatesintheIL3-mediatedRas-Erk,PI3K-Aktsignalingpathways.SoSHP-2couldbethekeyelementofthehighvalue-addedsignal-regulatedinmyeloidcellsandaimportantregulatoryinthepathog-enesisofmyeloproliferativedisorders.KeyWords:TyrosinephosphataseSHP-2;Cellsignalingpathway;Myeloproliferativedisorders英文缩略语缩略语英文名称中文全称AktBSAEDTAproteinkinaseB(PKB)BovineSerumAlbuminEthyleneDiamineTetraaceticAcid丝苏氨酸激酶牛血清白蛋白乙二胺四乙酸ERKFCMFITCGab2extracellularsignal-regulatedFlowCytometryFluoresceinisothiocyanateGRB2-associatedbinder-2胞外信号调节激酶流式细胞仪异硫氰酸荧光素Grb2相关结合蛋白2HRPhorseradishperoxidase辣根过氧化物酶IL-3Interleukin-3白细胞介素-3IRSinsulinreceptorsubstrate胰岛素受体底物MAPKMitogen-ActivatedProteinKinase丝裂原活化蛋白激酶MEFsMouseEmbryonicFibroblasts小鼠胚胎成纤维细胞mMmillimole／liter毫摩尔／升NF-κBnuclearfactorkappaB核转录因子κBPBSphosphatebufferedsolution中性磷酸盐缓冲溶液PDGFRplatelet-derivedgrowthfactorreceptor血小板衍生生长因子受体PI3K3-hydroxy-phosphatidylinositolkinase3-羟基磷脂酰肌醇激酶ScfStemcellgrowthfactor干细胞生长因子SDSSodiumdodecylsulfate十二烷基