Casein kinase I transduces Wnt signals

• Published in: Nature (London) Vol. 401; no. 6751; pp. 345 - 350
• Main Authors: Graff, Jonathan M, Peters, John M, McKay, Renée M, McKay, James P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 23.09.1999; Nature Publishing Group
• Subjects: Adaptor Proteins, Signal Transducing; Animals; beta Catenin; Biological and medical sciences; Blocking; Caenorhabditis elegans; Casein; Casein Kinases; Classical genetics, quantitative genetics, hybrids; Cloning; Cloning, Molecular; Cytoskeletal Proteins - metabolism; Dishevelled Proteins; Embryo, Nonmammalian - enzymology; Embryo, Nonmammalian - metabolism; Enzyme Inhibitors - pharmacology; Epistasis, Genetic; Fundamental and applied biological sciences. Psychology; Genes; Genetics of eukaryotes. Biological and molecular evolution; Isoquinolines - pharmacology; Kinases; Molecular biology; Molecular Sequence Data; Mutation; Pathways; Phosphoproteins - metabolism; Phosphorylation; Protein Binding; Protein Kinase Inhibitors; Protein Kinases - genetics; Protein Kinases - metabolism; Proto-Oncogene Proteins - metabolism; Signal Transduction; Signalling; Trans-Activators; Vertebrata; Vertebrates; Wnt Proteins; Xenopus; Xenopus Proteins; Zebrafish Proteins; Embryonic development; Phosphorylation; Enzyme; Transferases; Xenopus laevis; Amphibia; Enzyme inhibitor; Salientia; Gene expression; Morphogenesis; Signal transduction; Vertebrata; Gene; Protein kinase
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/43830

The Wnt signalling cascade is essential for the development of both invertebrates and vertebrates, and is altered during tumorigenesis. Although a general framework for Wnt signalling has been elucidated, not all of the components have been identified. Here we describe a serine kinase, casein kinase I (CKI), which was isolated by expression cloning in Xenopus embryos. CKI reproduces several properties of Wnt signals, including generation of complete dorsal axes, stabilization of beta-catenin and induction of genes that are direct targets of Wnt signals. Dominant-negative forms of CKI and a pharmacological blocker of CKI inhibited Wnt signals in Xenopus. Inhibiting CKI in Caenorhabditis elegans generated worms with a mom phenotype, indicative of a loss of Wnt signals. In addition, CKI bound to and increased the phosphorylation of dishevelled, a known component of the Wnt pathway. These data indicate that CKI may be a conserved component of the Wnt pathway.