Casein kinase I transduces Wnt signals

Nature. 1999 Sep 23;401(6751):345-50. doi: 10.1038/43830.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Caenorhabditis elegans
  • Casein Kinases
  • Cloning, Molecular
  • Cytoskeletal Proteins / metabolism
  • Dishevelled Proteins
  • Embryo, Nonmammalian / enzymology
  • Embryo, Nonmammalian / metabolism
  • Enzyme Inhibitors / pharmacology
  • Epistasis, Genetic
  • Isoquinolines / pharmacology
  • Molecular Sequence Data
  • Mutation
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Kinase Inhibitors
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Signal Transduction*
  • Trans-Activators*
  • Wnt Proteins
  • Xenopus
  • Xenopus Proteins
  • Zebrafish Proteins*
  • beta Catenin

Substances

  • Adaptor Proteins, Signal Transducing
  • CTNNB1 protein, Xenopus
  • Cytoskeletal Proteins
  • Dishevelled Proteins
  • Enzyme Inhibitors
  • Isoquinolines
  • Phosphoproteins
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Wnt Proteins
  • Xenopus Proteins
  • Zebrafish Proteins
  • beta Catenin
  • N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide
  • Protein Kinases
  • Casein Kinases

Associated data

  • GENBANK/AF183394