Schistosoma mansoni TGF-β Receptor II Role in Host Ligand-Induced Regulation of a Schistosome Target Gene 英文参考文献.docVIP

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Schistosoma mansoni TGF-β Receptor II Role in Host Ligand-Induced Regulation of a Schistosome Target Gene 英文参考文献.doc

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SchistosomamansoniTGF-bReceptorII: RoleinHostLigand-InducedRegulation ofaSchistosomeTargetGene Ahmed Osman1,Edward G.Niles1,Sergio Verjovski-Almeida2,Philip T.LoVerde1,3* 1DepartmentofMicrobiologyandImmunology,SchoolofMedicineandBiomedicalSciences,StateUniversityofNewYorkatBuffalo,Buffalo,NewYork,UnitedStatesof America,2DepartamentodeBioqu?′mica,InstitutodeQu?′mica,UniversidadedeSa?oPaulo,Sa?oPaulo,Brazil,3SouthwestFoundationforBiomedicalResearch,SanAntonio, Texas,UnitedStatesofAmerica Members of transforming growth factor-beta (TGF-b) superfamily play pivotal roles in development in multicellular organisms.WereportthefunctionalcharacterizationoftheSchistosomamansonitypeIIreceptor(SmTbRII).Miningof the S. mansoni expressed sequence tag (EST) database identified an EST clone that shows homology to the kinase domainoftypeIIreceptorsfromdifferentspecies.TheamplifiedESTsequencewasusedasaprobetoisolateacDNA clonespanningtheentirecodingregionofatypeIIserine/threoninekinasereceptor.TheinteractionofSmTbRIIwith SmTbRIwaselucidatedandshowntobedependentonTGF-bligandbinding.Furthermore,inthepresenceofhuman TGF-b1, SmTbRII was able to activate SmTbRI, which in turn activated SmSmad2 and promoted its interaction with SmSmad4,provingthetransferofthesignalfromthereceptor complextotheSmadproteins. Gynaecophoralcanal protein(GCP),whoseexpressioninmalewormsislimitedtothegynaecophoriccanal,wasidentifiedasapotentialTGF- btargetgeneinschistosomes.KnockingdowntheexpressionofSmTbRIIusingshortinterferingRNAmolecules(siRNA) resultedinaconcomitantreductionintheexpressionofGCP.Thesedataprovideevidenceforthedirectinvolvement ofSmTbRIIinmediatingTGF-b–inducedactivationoftheTGF-btargetgene,SmGCP,withinschistosomeparasites.The results also provide additional evidence for a role for the TGF-b signaling pathway in male-induced female reproductivedevelopment. Citation:OsmanA,NilesEG,Verjovski-AlmeidaS,LoVerdePT(2006)SchistosomamansoniTGF-breceptorII:Roleinhostligand-inducedregulationofasch