Short Stat5-Interacting Peptide Derived from Phospholipase C-β3 Inhibits Hematopoietic Cell Proliferation and Myeloid Differentiation 英文参考文献.docVIP

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Short Stat5-Interacting Peptide Derived from Phospholipase C-β3 Inhibits Hematopoietic Cell Proliferation and Myeloid Differentiation 英文参考文献.doc

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ShortStat5-InteractingPeptideDerivedfrom PhospholipaseC-b3InhibitsHematopoieticCell ProliferationandMyeloidDifferentiation HirokiYasudo,TomoakiAndo,WenbinXiao¤,YukoKawakami,ToshiakiKawakami* DivisionofCellBiology,LaJollaInstituteforAllergyandImmunology,LaJolla,California,UnitedStatesofAmerica Abstract Constitutive activation of the transcription factor Stat5 in hematopoietic stem/progenitor cells leads to various hematopoietic malignancies includingmyeloproliferative neoplasm (MPN). Ourrecentstudy foundthatphospholipase C (PLC)-b3isanoveltumorsuppressorinvolvedinMPN,lymphomaandothertumors.Stat5activityisnegativelyregulatedby the SH2 domain-containing protein phosphatase SHP-1 in a PLC-b3-dependent manner. PLC-b3 can form the multimolecular SPS complex together with SHP-1 and Stat5. The close physical proximity of SHP-1 and Stat5 brought aboutbyinteractingwiththeC-terminalsegmentofPLC-b3(PLC-b3-CT)acceleratesSHP-1-mediateddephosphorylationof Stat5. Here we identify the minimal sequences within PLC-b3-CT required for its tumor suppressor function. Two of the threeStat5-bindingnoncontiguousregions,oneofwhichalsobindsSHP-1,substantiallyinhibitedinvitroproliferationof Ba/F3cells.Surprisingly,an11-residueStat5-bindingpeptide(residues988-998)suppressedStat5activityinBa/F3cellsand invivoproliferationandmyeloiddifferentiationofhematopoieticstem/progenitorcells.Therefore,thisstudyfurtherdefines PLC-b3-CT as the Stat5- andSHP-1-binding domain by identifying minimal functional sequences of PLC-b3 for its tumor suppressorfunctionandimpliestheirpotentialutilityinthecontrolofhematopoieticmalignancies. Citation:YasudoH,AndoT,XiaoW,KawakamiY,KawakamiT(2011)ShortStat5-InteractingPeptideDerivedfromPhospholipaseC-b3InhibitsHematopoietic CellProliferationandMyeloidDifferentiation.PLoSONE6(9):e24995.doi:10.1371/journal.pone.0024995 Editor:MariaG.Castro,UniversityofMichiganSchoolofMedicine,UnitedStatesofAmerica ReceivedMay27,2011;AcceptedAugust22,2011;PublishedSeptember20,2011 Copyri