R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6

被引：223

作者：

Binnerts, Minke E. ^{[1
]}

Kim, Kyung-Ah ^{[1
]}

Bright, Jessica M. ^{[1
]}

Patel, Sejal M. ^{[1
]}

Tran, Karolyn ^{[1
]}

Zhou, Mei ^{[1
]}

Leung, John M. ^{[1
]}

Liu, Yi ^{[1
]}

Lomas, Woodrow E., III ^{[1
]}

Dixon, Melissa ^{[1
]}

Hazell, Sophie A. ^{[1
]}

Wagle, Marie ^{[1
]}

Nie, Wen-Sheng ^{[1
]}

Tomasevic, Nenad ^{[1
]}

Williams, Jason ^{[1
]}

Zhan, Xiaoming ^{[1
]}

Levy, Michael D. ^{[1
]}

Funk, Walter D. ^{[1
]}

Abo, Arie ^{[1
]}

机构：

[1] Nuvelo Inc, San Carlos, CA 94070 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2007年 / 104卷 / 37期

关键词：

beta-catenin; DKK1; kremen;

D O I：

10.1073/pnas.0702305104

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The R-Spondin (RSpo) family of secreted proteins act as potent activators of the Wnt/beta-catenin signaling pathway. We have previously shown that RSpo proteins can induce proliferative effects on the gastrointestinal epithelium in mice. Here we provide a mechanism whereby RSpo1 regulates cellular responsiveness to Writ ligands by modulating the cell-surface levels of the coreceptor LRP6. We show that RSpo1 activity critically depends on the presence of canonical Writ ligands and LRP6. Although RSpo1 does not directly activate LRP6, it interferes with DKK1/Kremen-mediated internalization of LRP6 through an interaction with Kremen, resulting in increased LRP6 levels on the cell surface. Our results support a model in which RSpo1 relieves the inhibition DKK1 imposes on the Writ pathway.

引用

收藏

页码：14700 / 14705

页数：6

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