黑色素瘤相关抗原MAAT1p15与LRP6的相互作用及其对Wnt信号通路的调控  

MAAT1 p15 Interacts with LRP6 and Regulates Wnt Signaling Pathway

作　　者：韩亮[1] 张新军[1] 黄世思[1] 翟永功[2] 常智杰[1] 

机构地区：[1]清华大学生物科学与技术系,人类基因组研究所,清华大学生命科学与医学研究院,北京100084 [2]北京师范大学,生命科学学院,生物医学研究所,北京100875

出　　处：《中国生物化学与分子生物学报》2004年第6期827-832,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目 (No .3 0 2 2 80 0 7和No .3 0 0 70 70 3 );清华大学985项目联合资助~~

摘　　要：为了深入研究Wnt信号的传导机制 ,利用GAL4酵母双杂交系统 ,以Wnt受体LRP6的胞内区为诱饵蛋白 ,筛选小鼠 11 5d胚胎cDNA文库 ,发现了一个新的LRP6相互作用蛋白 :黑色素瘤相关抗原MAAT1p15 (melanoma associatedantigenrecognizedbycytotoxicTlymphocytesp15 ) .免疫共沉淀方法证明了LRP6胞内区和MAAT1p15在哺乳动物细胞中也存在相互作用 .荧光素酶报告系统分析实验显示 ,MAAT1p15能够明显增强Wnt1和LRP6响应的下游基因的转录活性 。To investigate the mechanism of Wnt signaling pathway,an 11.5 day mouse embryo cDNA library was screened for interacting proteins of LRP6, a coreceptor in canonical Wnt signaling pathway, by yeast two-hybrid experiment. One of the positive clones was identified as MAAT1 p15 (melanoma-associated antigen recognized by cytotoxic T lymphocytes p15) and the interaction between these two proteins was confirmed by co-immunoprecipitation assay in mammalian cells. Futhermore, the result from luciferase assay demonstrated that MAAT1 p15 increased Wnt1 and LRP6 induced transcriptional activity of reporter gene driven by LEF-1, a downstream transcriptional factor in Wnt signaling pathway. These results suggested that MAAT1 p15 could regulate Wnt signaling pathway through interaction with LRP6 and might be involved in Wnt singal transduction related to melanoma.

关 键 词：WNT RP6 MAAT1 P15 酵母双杂交 免疫共沉淀 荧光素酶报告系统 

分 类 号：Q78[生物学—分子生物学]