Dapper, a Dishevelled-associated antagonist of β-catenin and JNK signaling, is required for notochord formation
Dapper, a Dishevelled-associated antagonist of β-catenin and JNK signaling, is required for notochord formation
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DOI：
10.1016/s1534-5807(02)00140-5
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发表时间：
2002-04-01
影响因子：
11.8
通讯作者：
Moon, RT
中科院分区：
文献类型：
--
作者：
Cheyette, BNR;Waxman, JS;Moon, RT
Dapper是在筛选与disheveled相互作用的蛋白中分离出来的，disheveled是Wnt信号传导的关键因子。Dapper和disheveled在细胞内共定位，并与Axin、GSK-3、CKI和β -连环蛋白形成复合物。过表达Dapper会增加该复合体中的Axin和GSK-3，导致可溶性β -连环蛋白减少和β -连环蛋白应答基因的激活减少。Dapper还可以抑制c-Jun n-末端激酶（JNK）的散乱激活，JNK是β -连环蛋白非依赖性卷曲信号的一个组成部分。抑制Dapper激活β -连环蛋白应答基因和ap1应答启动子，表明Dapper是一种通用的disheveled拮抗剂。爪蟾胚胎中母体Dapper RNA的缺失导致脊索和头部结构的缺失，这表明Dapper是正常脊椎动物发育所必需的。
Dapper was isolated in a screen for proteins interacting with Dishevelled, a key factor in Wnt signaling. Dapper and Dishevelled colocalize intracellularly and form a complex with Axin, GSK-3, CKI, and beta-catenin. Overexpression of Dapper increases Axin and GSK-3 in this complex, resulting in decreased soluble beta-catenin and decreased activation of beta-catenin-responsive genes. Dapper also inhibits activation by Dishevelled of c-Jun N-terminal kinase (JNK), a component of beta-catenin-independent Frizzled signaling. Inhibition of Dapper activates both beta-catenin-responsive genes and an AP1-responsive promoter, demonstrating that Dapper is a general Dishevelled antagonist. Depletion of maternal Dapper RNA from Xenopus embryos results in loss of notochord and head structures, demonstrating that Dapper is required for normal vertebrate development.