title: 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 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.
authors: Division of Molecular Embryology, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
authors: Cristina-Maria
authors: CM
authors: Cruciat
authors: Christine
authors: C
authors: Dolde
authors: Reinoud E A
authors: RE
authors: de Groot
authors: Bisei
authors: B
authors: Ohkawara
authors: Carmen
authors: C
authors: Reinhard
authors: Hendrik C
authors: HC
authors: Korswagen
authors: Christof
authors: C
authors: Niehrs
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D048149:Casein Kinase 1 epsilon / Q000737:chemistry / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072261:Dishevelled Proteins; D057809:HEK293 Cells; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D014981:Xenopus / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051176:beta Catenin; D048149:Casein Kinase 1 epsilon; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases