Casein kinase I transduces Wnt signals.
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.
Peters
J M
JM
Center for Developmental Biology, Department of Molecular Biology, UT Southwestern Medical Center, Dallas, Texas 75235-9133, USA. graff02@utsw.swmed.edu
McKay
R M
RM
McKay
J P
JP
Graff
J M
JM
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017173:Caenorhabditis elegans; D047388:Casein Kinases; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000378:metabolism; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian / Q000201:enzymology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004843:Epistasis, Genetic; D007546:Isoquinolines / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators; D051153:Wnt Proteins; D014981:Xenopus; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; C495266:CTNNB1 protein, Xenopus; D003598:Cytoskeletal Proteins; D000072261:Dishevelled Proteins; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C058815:N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide; D011494:Protein Kinases; D047388:Casein Kinases