A BCR-ABL Mutant Lacking Direct Binding Sites for the GRB2, CBL and CRKL Adapter Proteins Fails to Induce Leukemia in Mice 英文参考文献.docVIP

下载本文档

2
0
约5.89万字
约 11页
2017-05-11 发布于上海
举报
版权申诉

A BCR-ABL Mutant Lacking Direct Binding Sites for the GRB2, CBL and CRKL Adapter Proteins Fails to Induce Leukemia in Mice 英文参考文献.doc

1、本文档共11页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

A BCR-ABL Mutant Lacking Direct Binding Sites for the GRB2, CBL and CRKL Adapter Proteins Fails to Induce Leukemia in Mice 英文参考文献

ABCR-ABLMutantLackingDirectBindingSitesforthe GRB2,CBLandCRKLAdapterProteinsFailstoInduce LeukemiainMice KaraJ.Johnson1*,IanJ.Griswold1,3,ThomasO’Hare1,3,AmieS.Corbin1,3,MarcLoriaux2,MichaelW. Deininger1,BrianJ.Druker1,3 1DivisionofHematologyandMedicalOncology,OregonHealthScienceUniversityKnightCancerInstitute,Portland,Oregon,UnitedStatesofAmerica,2Departmentof Pathology, Oregon Health Science University, Portland, Oregon, United States of America, 3Howard Hughes Medical Institute, Oregon Health Science University KnightCancerInstitute,Portland,Oregon,UnitedStatesofAmerica Abstract TheBCR-ABLtyrosinekinaseisthedefiningfeatureofchronicmyeloidleukemia(CML)anditskinaseactivityisrequiredfor induction of this disease. Current thinking holds that BCR-ABL forms a multi-protein complex that incorporates several substrates and adaptor proteins and is stabilized by multiple direct and indirect interactions. Signaling output from this highlyredundantnetworkleadstocellulartransformation.ProteinsknowntobeassociatedwithBCR-ABLinthiscomplex include: GRB2, c-CBL, p62DOK, and CRKL. These proteins in turn, link BCR-ABL to various signaling pathways indicated in cellulartransformation.InthisstudyweshowthatatriplemutantofBCR-ABLwithmutationsofthedirectbindingsitesfor GRB2,CBL,p62DOK andCRKL,isdefectivefortransformationofprimaryhematopoieticcellsinvitroandinamurineCML model,whileitretainsthecapacitytoinduceIL-3independencein32Dcells.ComparedtoBCR-ABL,thetriplemutant’s ability to activate the MAP kinase and PI3-kinase pathways is severely compromised, while STAT5 phosphorylation is maintained, suggesting that the former are crucial for the transformation of primary cells, but dispensable for transformationoffactordependentcelllines.OurdatasuggestthatinhibitionofBCR-ABL-inducedleukemiabydisrupting proteininteractionscouldbepossible,butwouldrequireblockingofmultiplesites. Citation:JohnsonKJ,GriswoldIJ,O’HareT,CorbinAS,LoriauxM,etal.(2009)ABCR-ABLMutantLackingDirectBindingSitesfortheG