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  Negative regulation of Wnt signaling mediated by CK1-phosphorylated Dishevelled via Ror2.

Witte, F., Bernatik, O., Kirchner, K., Masek, J., Mahl, A., Krejci, P., et al. (2010). Negative regulation of Wnt signaling mediated by CK1-phosphorylated Dishevelled via Ror2. The FASEB Journal, 24(7), 2417-2426. doi:10.1096/fj.09-150615.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7BEC-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7BED-6
Genre: Journal Article
Alternative Title : FASEB J

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 Creators:
Witte, F.1, Author              
Bernatik, O., Author
Kirchner, K., Author
Masek, J., Author
Mahl, A., Author
Krejci, P., Author
Mundlos, S.2, Author              
Schambony, A., Author
Bryja, V., Author
Stricker, S.2, Author              
Affiliations:
1Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433547              
2Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              

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Free keywords: Wnt/β-catenin signaling; casein kinase; Wnt5a; Xenopus
 Abstract: Dishevelled (Dvl) is a multifunctional effector of different Wnt cascades. Both canonical Wnt3a and noncanonical Wnt5a stimulate casein-kinase-1 (CK1) -mediated phosphorylation of Dvl, visualized as electrophoretic mobility shift [phosphorylated and shifted Dvl (ps-Dvl)]. However, the role of this phosphorylation remains obscure. Here we report the functional interaction of ps-Dvl with the receptor tyrosine kinase Ror2, which is an alternative Wnt receptor and is able to inhibit canonical Wnt signaling. We demonstrate interaction between Ror2 and ps-Dvl at the cell membrane after Wnt3a or Wnt5a stimulus dependent on CK1. Ps-Dvl interacts with the C-terminal proline-serine-threonine-rich domain of Ror2, which is required for efficient inhibition of canonical Wnt signaling. We further show that the Dvl C terminus, which seems to be exposed in ps-Dvl and efficiently binds Ror2, is an intrinsic negative regulator of the canonical Wnt pathway downstream of beta-catenin. The Dvl C terminus is necessary and sufficient to inhibit canonical Wnt/beta-catenin signaling, which is dependent on the presence of Ror2. Furthermore, both the Dvl C terminus and CK1epsilon can inhibit the Wnt5a/Ror2/ATF2 pathway in mammalian cells and Xenopus explant cultures. This suggests that phosphorylation of Dvl triggers negative feedback regulation for different branches of Wnt signaling in a Ror2-dependent manner.

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Language(s): eng - English
 Dates: 2010-02-04
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
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Title: The FASEB Journal
  Alternative Title : FASEB J
Source Genre: Journal
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Pages: - Volume / Issue: 24 (7) Sequence Number: - Start / End Page: 2417 - 2426 Identifier: ISSN: 0892-6638