Dapper是一种与Dishevelled相关的β-连环蛋白和JNK信号通路拮抗剂，是脊索形成所必需的。

Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK signaling, is required for notochord formation.

作者信息

Cheyette Benjamin N R, Waxman Joshua S, Miller Jeffrey R, Takemaru Ken-Ichi, Sheldahl Laird C, Khlebtsova Natasha, Fox Eric P, Earnest Thomas, Moon Randall T

机构信息

Howard Hughes Medical Institute, Department of Pharmacology and Center for Developmental Biology, University of Washington School of Medicine, Seattle, WA 98195, USA.

出版信息

Dev Cell. 2002 Apr;2(4):449-61. doi: 10.1016/s1534-5807(02)00140-5.

DOI:10.1016/s1534-5807(02)00140-5

PMID:11970895

Abstract

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.

摘要

在一项针对与Dishevelled（Wnt信号通路中的关键因子）相互作用的蛋白质的筛选中，发现了Dapper。Dapper与Dishevelled在细胞内共定位，并与Axin、GSK-3、CKI和β-连环蛋白形成复合物。Dapper的过表达增加了该复合物中Axin和GSK-3的含量，导致可溶性β-连环蛋白减少以及β-连环蛋白反应性基因的激活减少。Dapper还抑制了Dishevelled对c-Jun N端激酶（JNK，β-连环蛋白非依赖性卷曲蛋白信号通路的一个组成部分）的激活。抑制Dapper会激活β-连环蛋白反应性基因和AP1反应性启动子，表明Dapper是一种普遍的Dishevelled拮抗剂。从非洲爪蟾胚胎中去除母源Dapper RNA会导致脊索和头部结构缺失，表明Dapper是正常脊椎动物发育所必需的。