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dc.contributor.authorLuo, W.zh_CN
dc.contributor.authorNg, W. W.zh_CN
dc.contributor.authorJin, L. H.zh_CN
dc.contributor.authorYe, Z. Y.zh_CN
dc.contributor.authorHan, J. H.zh_CN
dc.contributor.authorLin, S. C.zh_CN
dc.contributor.author林圣彩zh_CN
dc.date.accessioned2013-12-12T02:24:13Z
dc.date.available2013-12-12T02:24:13Z
dc.date.issued2003-09-26zh_CN
dc.identifier.citationJournal of Biological Chemistry, 2003,278(39):37451-37458zh_CN
dc.identifier.issn0021-9258zh_CN
dc.identifier.otherISI:000185437200057zh_CN
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/65311
dc.description.abstractAxin is a multidomain protein that plays a critical role in Wnt signaling, serving as a scaffold for down-regulation of beta-catenin. It also activates the JNK mitogen-activated protein kinase by binding to MEKK1. However, it is intriguing that Axin requires several additional elements for JNK activation, including a requirement for homodimerization, sumoylation at the extreme C-terminal sites, and a region in the protein phosphatase 2A-binding domain. In our present study, we have shown that another MEKK family member, MEKK4, also binds to Axin in vivo and mediates Axin-induced JNK activation. Surprisingly MEKK4 binds to a region distinct from the MEKK1-binding site. Dominant negative mutant of MEKK4 attenuates the JNK activation by Axin. Activation of JNK by Axin in MEKK1(-/-) mouse embryonic fibroblast cells supports the idea that another MEKK can mediate Axin-induced JNK activation. Expression of specific small interfering RNA against MEKK4 effectively attenuates JNK activation by the MEKK1 binding-defective Axin mutant in 293T cells and inhibits JNK activation by wild-type Axin in MEKK1(-/-) cells, confirming that MEKK4 is indeed another mitogen-activated protein kinase kinase kinase that is specifically involved in Axin-mediated JNK activation independently of MEKK1. We have also identified an additional domain between MEKK1- and MEKK4-binding sites as being required for JNK activation by Axin. MEKK1 and MEKK4 compete for Axin binding even though they bind to sites far apart, suggesting that Axin may selectively bind to MEKK1 or MEKK4 depending on distinct signals or cellular context. Our findings will provide new insights into how scaffold proteins mediate ultimate activation of different mitogen-activated protein kinase kinase kinases.zh_CN
dc.language.isoen_USzh_CN
dc.source.urihttp://dx.doi.org/10.1074/jbc.M305277200zh_CN
dc.subjectWNT SIGNALING PATHWAYzh_CN
dc.subjectCASEIN KINASE-Izh_CN
dc.subjectMIXED-LINEAGE KINASEzh_CN
dc.subjectPROTEIN-KINASEzh_CN
dc.subjectBETA-CATENINzh_CN
dc.subjectNEGATIVE REGULATORzh_CN
dc.subjectRNA INTERFERENCEzh_CN
dc.subjectGENE DISRUPTIONzh_CN
dc.subjectMAMMALIAN-CELLSzh_CN
dc.subjectEXPRESSIONzh_CN
dc.titleAxin utilizes distinct regions for competitive MEKK1 and MEKK4 binding and JNK activationzh_CN
dc.typeArticlezh_CN


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