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

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Details zur Publikation

Autorinnen und Autoren: Witte F, Bernatik O, Kirchner K, Masek J, Mahl A, Krejci P, Mundlos S, Schambony A, Bryja V, Stricker S
Zeitschrift: FASEB Journal
Jahr der Veröffentlichung: 2010
Band: 24
Heftnummer: 7
Seitenbereich: 2417-2426
ISSN: 0892-6638
eISSN: 1530-6860


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.

FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Kirchner, Katharina
Lehrstuhl für Entwicklungsbiologie
Schambony, Alexandra Prof. Dr.
Lehrstuhl für Entwicklungsbiologie

Einrichtungen weiterer Autorinnen und Autoren

Masaryk University
Max-Planck-Institut für molekulare Genetik / Max Planck Institute for Molecular Genetics


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. FASEB Journal, 24(7), 2417-2426.

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


Zuletzt aktualisiert 2018-06-08 um 20:40