RNA Helicase DDX3 Is a Regulatory Subunit of Casein Kinase 1 in Wnt-β-Catenin Signaling
Abstract
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 CK1ɛ: In a Wnt-dependent manner, DDX3 binds CK1ɛ 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.
- Publication:
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Science
- Pub Date:
- March 2013
- DOI:
- 10.1126/science.1231499
- Bibcode:
- 2013Sci...339.1436C
- Keywords:
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- CELL BIOL Cell-Biology, Molecular-Biology, Biochemistry