Wnt-independent activation of β-catenin mediated by a Dkk1-Fz5 fusion protein

被引：37

作者：

Holmen, SL ^{[1
]}

Robertson, SA ^{[1
]}

Zylstra, CR ^{[1
]}

Williams, BO ^{[1
]}

机构：

[1] Van Andel Res Inst, Lab Cell Signaling & Carinogenesis, Grand Rapids, MI 49503 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2005年 / 328卷 / 02期

关键词：

Wnt signaling; Lrp5; Lrp6; Dkk I; frizzled; dishevelled; Wnt;

D O I：

10.1016/j.bbrc.2005.01.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

An XWnt8-Fz5 fusion protein synergizes with LRP6 to potently activate P-catenin-dependent signaling. Here, we generated a fusion in which XWnt8 was fused to the N-terminus of LRP6 and show it synergizes with both Fz4 and Fz5 to potently transactivate beta-catenin-dependent Wnt signaling. Based on this, we hypothesized that the main function of Wnt is to nucleate the formation of a physical complex between LRP6 and a Frizzled. Dkk1, but not the related Dkk3, binds LRP6 and inhibits canonical Wnt signaling by blocking the interaction of Wnt and LRP6. Therefore, we reasoned that a covalent fusion of Dkk1 to Fz5 (Dkk1-Fz5) would mimic Wnt ligand by nucleating the formation of a complex containing Fz5 and LRP6, while Dkk3 (Dkk3-Fz5) would not. We found that Dkk1-Fz5, but not Dkk3-Fz5, potently synergized with LRP6 to activate signaling in a dishevelled-dependent manner. (C) 2005 Elsevier Inc. All rights reserved.

引用

页码：533 / 539

页数：7

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