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 CK1ε: In a Wnt-dependent manner, DDX3 binds CK1ε 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 types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / growth & development
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Caenorhabditis elegans / metabolism
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism
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Casein Kinase 1 epsilon / chemistry
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Casein Kinase 1 epsilon / metabolism*
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DEAD-box RNA Helicases / chemistry
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DEAD-box RNA Helicases / genetics
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DEAD-box RNA Helicases / metabolism*
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Dishevelled Proteins
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HEK293 Cells
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Humans
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Phosphoproteins / metabolism
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Phosphorylation
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Protein Binding
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Protein Structure, Tertiary
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RNA Helicases / chemistry
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RNA Helicases / genetics
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RNA Helicases / metabolism*
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Wnt Proteins / metabolism
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Wnt Signaling Pathway*
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Xenopus / embryology
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Xenopus / genetics
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Xenopus / metabolism
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Xenopus Proteins / chemistry
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Xenopus Proteins / genetics
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Xenopus Proteins / metabolism*
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beta Catenin / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Caenorhabditis elegans Proteins
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Dishevelled Proteins
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Phosphoproteins
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Wnt Proteins
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Xenopus Proteins
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beta Catenin
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Casein Kinase 1 epsilon
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DDX3X protein, human
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DEAD-box RNA Helicases
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RNA Helicases