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

被引：215

作者：

Cheyette, BNR

Waxman, JS

Miller, JR

Takemaru, KI

Sheldahl, LC

Khlebtsova, N

Fox, EP

Earnest, T

Moon, RT ^{[1
]}

机构：

[1] Univ Washington, Sch Med, Dept Pharmacol, Howard Hughes Med Inst, Seattle, WA 98195 USA

[2] Univ Washington, Sch Med, Ctr Dev Biol, Seattle, WA 98195 USA

[3] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA

[4] Univ Calif Berkeley, Lawrence Berkeley Lab, Phys Biosci Div, Berkeley Ctr Struct Biol, Berkeley, CA 94720 USA

来源：

DEVELOPMENTAL CELL | 2002年 / 2卷 / 04期

关键词：

D O I：

10.1016/S1534-5807(02)00140-5

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：449 / 461

页数：13

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[1] Interaction between wingless and notch signaling pathways mediated by dishevelled [J].