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Casein kinase I transduces Wnt signals

Nature volume 401, pages 345–350 (1999)Cite this article

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 β-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.

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Figure 1: CKI produces complete secondary dorsal axes.
Figure 2: CKI stabilizes β-catenin and induces the expression of Wnt-specific markers.
Figure 3: Blocking CKI inhibits Wnt signalling in Xenopus.
Figure 4: CKI RNA interference produces the mom phenotype in C. elegans.
Figure 5: CKI functions between dishevelled and GSK-3.
Figure 6: CKI binds to and increases the phosphorylation of dishevelled.

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Acknowledgements

We thank L. Avery, M. Henkemeyer, J. Jiang, R. Lalan, L. Meng, L. Parada, and members of the Graff lab for support and comments. We also thank X. Cao, M. Cobb, F. Constantini (axin), C. Cowan, R. Harland (Xwnt-8, β-galactosidase, pCS105), J. Heasman, D. Kessler, D. Kimelman (GBP, GSK-3), P. Klein (XFz8, Nfz), R. Lin, R. Moon, B. Powell (mouse neonatal brain yeast two-hybrid library), J. Priess (3NB12 and ICB4 antibodies), S. Sokol (Xdsh, Xdd1), D. Turner (pCS2 + MT), and C. Wylie (β-catenin) for providing reagents and technical advice. J.P.M. was supported by NIH and Established Investigator AHA awards to L. Avery, in whose laboratory the C. elegans experiments were conducted. This work was supported by an NIH award to J.M.G. J.M.G. is a March of Dimes Basil O'Connor Scholar and a Charles E. Culpeper Medical Scholar.

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  1. John M. Peters and Renée M. McKay: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Molecular Biology, Center for Developmental Biology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, NB 5.208, Dallas, 75235-9133, Texas, USA

    John M. Peters, Renée M. McKay & Jonathan M. Graff

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Correspondence to Jonathan M. Graff.

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Peters, J., McKay, R., McKay, J. et al. Casein kinase I transduces Wnt signals. Nature 401, 345–350 (1999). https://doi.org/10.1038/43830

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