ARHGEF7 (BETA-PIX) Acts as Guanine Nucleotide Exchange Factor for Leucine-Rich Repeat Kinase 2 英文参考文献.docVIP

下载本文档

9
0
约4.68万字
约 12页
2017-05-11 发布于上海
举报
版权申诉

ARHGEF7 (BETA-PIX) Acts as Guanine Nucleotide Exchange Factor for Leucine-Rich Repeat Kinase 2 英文参考文献.doc

1、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。。
2、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。
3、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)。
4、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
5、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。
6、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。
7、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

ARHGEF7 (BETA-PIX) Acts as Guanine Nucleotide Exchange Factor for Leucine-Rich Repeat Kinase 2 英文参考文献

ARHGEF7(BETA-PIX)ActsasGuanineNucleotide ExchangeFactorforLeucine-RichRepeatKinase2 KarinaHaebig1,ChristianJohannesGloeckner2,3,MartaGarciaMiralles4,FrankGillardon5 ,Claudia Schulte4,OlafRiess1,MariusUeffing2,3,SaskiaBiskup1,4*,MichaelBonin1* 1Institute of Human Genetics, Department of Medical Genetics, University of Tuebingen, Tuebingen, Germany, 2Department of Protein Science, Helmholtz-Zentrum Mu¨nchen,Munich,Germany,3CenterforOphthalmology,InstituteforOphthalmicResearch,UniversityofTuebingen,Tuebingen,Germany,4HertieInstituteforClinical BrainResearchandGermanCenterforNeurodegenerativeDiseases,UniversityofTuebingen,Tuebingen,Germany,5Boehringer-IngelheimPharmaGmbHCo.KG,CNS Research,BiberachanderRiss,Germany Abstract Background:Mutationswithintheleucine-richrepeatkinase2(LRRK2)geneareacommoncauseoffamilialandsporadic Parkinson’sdisease.ThemultidomainproteinLRRK2exhibitsoveralllowGTPaseandkinaseactivityinvitro. Methodology/PrincipalFindings:Here,weshowthattherhoguaninenucleotideexchangefactorARHGEF7andthesmall GTPaseCDC42areinteractingwithLRRK2invitroandinvivo.GTPaseactivityoffull-lengthLRRK2increasesinthepresence of recombinant ARHGEF7. Interestingly, LRRK2 phosphorylates ARHGEF7 in vitro at previously unknown phosphorylation sites.WeprovideevidencethatARHGEF7mightactasaguaninenucleotideexchangefactorforLRRK2andthatR1441C mutantLRRK2withreducedGTPhydrolysisactivityalsoshowsreducedbindingtoARHGEF7. Conclusions/Significance: Downstream effects of phosphorylation of ARHGEF7 through LRRK2 could be (i) a feedback controlmechanismforLRRK2activityaswellas(ii)animpactofLRRK2onactincytoskeletonregulation.Anewlyidentified familialmutationN1437S,localizedwithintheGTPasedomainofLRRK2,furtherunderlinestheimportanceoftheGTPase domainofLRRK2inParkinson’sdiseasepathogenesis. Citation:HaebigK,GloecknerCJ,MirallesMG,GillardonF,SchulteC,etal.(2010)ARHGEF7(BETA-PIX)ActsasGuanineNucleotideExchangeFactorforLeucine- RichRepeatKinase2.PLoSONE5(10):e13762.doi:10.1371/journal.pone.001376