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          Institute: MPI für molekulare Genetik     Collection: Research Group Development and Disease     Display Documents



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ID: 541114.0, MPI für molekulare Genetik / Research Group Development and Disease
Negative regulation of Wnt signaling mediated by CK1-phosphorylated Dishevelled via Ror2.
Authors:Witte, F.; Bernatik, O.; Kirchner, K.; Masek, J.; Mahl, A.; Krejci, P.; Mundlos, S.; Schambony, A.; Bryja, V.; Stricker, S.
Language:English
Date of Publication (YYYY-MM-DD):2010-02-04
Title of Journal:The FASEB Journal
Journal Abbrev.:FASEB J
Volume:24
Issue / Number:7
Start Page:2417
End Page:2426
Copyright:© 2010 by the Federation of American Societies for Experimental Biology
Review Status:not specified
Audience:Experts Only
Abstract / Description: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.
Free Keywords:Wnt/β-catenin signaling;
casein kinase;
Wnt5a;
Xenopus
Comment of the Author/Creator:Correspondence: S.S., Development and Disease Group,
Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195 Berlin, Germany. E-mail: strick_s@molgen.mpg.de; V.B., Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlářská 2, 61137 Brno, Czech Republic.
E-mail: bryja@sci.muni.cz
External Publication Status:published
Document Type:Article
Communicated by:Stefan Mundlos
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Institute for Medical Genetics, University Medicine Charité, Berlin, Germany;
2.Institut für Chemie/Biochemie, Freie Universität Berlin, Berlin, Germany;
3.Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic;
4.Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic;
5.Developmental Biology Unit, Biology Department, University of Erlangen-Nuremberg, Erlangen, Germany.
Identifiers:ISSN:0892-6638 [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/20215527 [ID No:2]
DOI:10.1096/fj.09-150615
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