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dc.contributor.authorMansky, K. C.zh_CN
dc.contributor.authorSankar, U.zh_CN
dc.contributor.authorHan, J. H.zh_CN
dc.contributor.authorOstrowski, M. C.zh_CN
dc.contributor.author韩家淮zh_CN
dc.date.accessioned2013-12-12T02:24:43Z
dc.date.available2013-12-12T02:24:43Z
dc.date.issued2002zh_CN
dc.identifier.citationJournal of Biological Chemistry,277(13):11077-11083zh_CN
dc.identifier.issn0021-9258zh_CN
dc.identifier.otherISI:000174613100043zh_CN
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/65815
dc.description.abstractReceptor activator of NF-kappaB ligand (RANKL) activates signaling pathways that regulate osteoclast differentiation, function, and survival. The microphthalmia transcription factor (MITF) is required for terminal differentiation of osteoclasts. To determine whether MITF could be a target of RANKL signaling, a phosphospecific MITF antibody directed against conserved residue Ser(307), a potential mitogen-activated protein kinase (MAPK) site, was produced. Using this antibody, we could demonstrate that MITF was rapidly and persistently phosphorylated upon stimulation of primary osteoclasts with RANKL and that phosphorylation of Ser(307) correlated with expression of the target gene tartrate-resistant acid phosphatase. MITF phosphorylation at Ser(307) also correlated with persistent activation of p38 MAPK, and p38 MAPK could utilize MITF Ser(307) as a substrate in vitro. The phosphorylation of MITF and activation of target gene expression in osteoclasts were blocked by p38 MAPK inhibitor SB203580. In transient transfections, a constitutively active Rac1 or MKK6 gene could collaborate with MITF to activate the tartrate-resistant acid phosphatase gene promoter dependent on Ser(307). Dominant negative p38 a and 0 could inhibit the collaboration between upstream signaling components and MITF in the transient assays. These results indicate that MITF is a target for the RANKL signaling pathway in osteoclasts and that phosphorylation of MITF leads to an increase in osteoclast-specific gene expression.zh_CN
dc.language.isoen_USzh_CN
dc.subjectLOOP-HELIX PROTEINzh_CN
dc.subjectMUSCLE DIFFERENTIATIONzh_CN
dc.subjectKINASEzh_CN
dc.subjectGENEzh_CN
dc.subjectOSTEOCLASTzh_CN
dc.subjectMEMBERzh_CN
dc.subjectFAMILYzh_CN
dc.subjectMOUSEzh_CN
dc.subjectINVOLVEMENTzh_CN
dc.subjectEXPRESSIONzh_CN
dc.titleMicrophthalmia transcription factor is a target of the p38 MAPK pathway in response to receptor activator of NF-kappa B ligand signalingzh_CN
dc.typeArticlezh_CN


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