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

Witte F, Bernatik O, Kirchner K, Masek J, Mahl A, Krejci P, Mundlos S, Schambony A, Bryja V, Stricker S (2010)

Publication Type: Journal article, Original article

Subtype: other

Publication year: 2010

Journal

The FASEB Journal Federation of American Society of Experimental Biology (FASEB)

Book Volume: 24

Pages Range: 2417-2426

Journal Issue: 7

URI: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=20215527&retmode=ref&cmd=prlinks

DOI: 10.1096/fj.09-150615

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.

Authors with CRIS profile

Katharina Kirchner Lehrstuhl für Entwicklungsbiologie Alexandra Schambony Lehrstuhl für Entwicklungsbiologie

Involved external institutions

Max-Planck-Institut für molekulare Genetik / Max Planck Institute for Molecular Genetics DE Germany (DE) Masaryk University CZ Czech Republic (CZ)

How to cite

APA:

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

MLA:

Witte, Florian, et al. "Negative regulation of Wnt signaling mediated by CK1-phosphorylated Dishevelled via Ror2." The FASEB Journal 24.7 (2010): 2417-2426.

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