Casein kinase I transduces Wnt signals

Author: Peters, J. M.; McKay, R. M.; McKay, J. P.; Graff, J. M.

Description: 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.

Subject headings: Adaptor Proteins; Signal Transducing; Animals; Caenorhabditis elegans; Casein Kinases; Cloning; Molecular; Cytoskeletal Proteins; Dishevelled Proteins; Embryo; Nonmammalian; Enzyme Inhibitors; Epistasis; Genetic; Isoquinolines; Molecular Sequence Data; Mutation; Phosphoproteins; Phosphorylation; Protein Binding; Protein Kinase Inhibitors; Protein Kinases; Proto-Oncogene Proteins; Signal Transduction; Trans-Activators; Wnt Proteins; Xenopus; Xenopus Proteins; Zebrafish Proteins; Beta Catenin

Publication year: 1999

Journal or book title: Nature

Volume: 401

Issue: 6751

Pages: 345-350

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Serial number: 3793

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