Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
RNA Helicase DDX3 Is a Regulatory Subunit of Casein Kinase 1 in Wnt–β-Catenin Signaling
Reinoud E. A. de Groot,2
Hendrik C. Korswagen,2
Casein kinase 1 (CK1) members play key roles in numerous biological processes. They are considered "rogue" kinases, because their enzymatic activity appears unregulated. Contrary to this notion, we have identified the DEAD-box RNA helicase DDX3 as a regulator of the Wnt–β-catenin network, where it acts as a regulatory subunit of CK1: In a Wnt-dependent manner, DDX3 binds CK1 and directly stimulates its kinase activity, and promotes phosphorylation of the scaffold protein dishevelled. DDX3 is required for Wnt–β-catenin signaling in mammalian cells and during Xenopus and Caenorhabditis elegans development. The results also suggest that the kinase-stimulatory function extends to other DDX and CK1 members, opening fresh perspectives for one of the longest-studied protein kinase families.
1 Division of Molecular Embryology, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. 2 Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Netherlands. 3 Institute of Molecular Biology, D-55128 Mainz, Germany.
* These authors contributed equally to this work.
Present address: Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Japan.
The editors suggest the following Related Resources on Science sites:
In Science Magazine
J. D. Berndt and R. T. Moon (22 March 2013) Science339 (6126), 1388.
[DOI: 10.1126/science.1236641] |Summary »|Full Text »|PDF »
In Science Signaling
Nancy R. Gough (26 March 2013) Sci. Signal.6 (268), ec73.
[DOI: 10.1126/scisignal.2004171] |Abstract »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Huwe1-Mediated Ubiquitylation of Dishevelled Defines a Negative Feedback Loop in the Wnt Signaling Pathway.
R. E. A. de Groot, R. S. Ganji, O. Bernatik, B. Lloyd-Lewis, K. Seipel, K. Šedova, Z. Zdrahal, V. M. Dhople, T. C. Dale, H. C. Korswagen, et al. (2014)
|Abstract »|Full Text »|PDF »
Casein Kinase 1 Regulates Sterol Regulatory Element-binding Protein (SREBP) to Control Sterol Homeostasis.