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Casein kinase I transduces Wnt signals
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.
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“Dsh is phosphorylated by a number of kinases including Casein Kinase 1,37 Casein Kinase 2,38 Metastasis Associated Kinase,39 Protein Kinase C40 and Par1.41”
From Wnt signal transduction pathways (2008) · cites this paper as [37]
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Control of β-Catenin Phosphorylation/Degradation by a Dual-Kinase Mechanism
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Metadata
- Authors
- Peters, J. M., McKay, R. M., McKay, J. P., & Graff, J. M.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Graff, Jonathan M.
- ORCID
- McKay, Renée M.
- Venue
- Nature
- Published
- 1999-09
- Volume
- 401
- Issue
- 6751
- Pages
- 345-350
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2114511731
- Cited by
- 447
- References
- 50
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 4 · 2023: 3 · 2022: 8 · 2021: 13 · 2020: 12 · 2019: 15 · 2018: 9 · 2017: 15 · 2016: 7 · 2015: 11 · 2014: 21 · 2013: 17 · 2012: 12
- FWCI
- 11.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Keywords
- casein kinase 1, Wnt signaling, signal transduction, β-catenin stabilization, dorsal axis formation, Xenopus embryo, dominant negative kinase, carcinogenesis
- MeSH terms
- Dishevelled Proteins, Animals, Cloning, Molecular, Cytoskeletal Proteins, Embryo, Nonmammalian, Enzyme Inhibitors, Epistasis, Genetic, Isoquinolines, Molecular Sequence Data, Mutation, Phosphoproteins, Phosphorylation, Protein Binding, Protein Kinases, Proto-Oncogene Proteins, Xenopus, Signal Transduction, Trans-Activators, Caenorhabditis elegans, Xenopus Proteins, Zebrafish Proteins, Casein Kinases, Protein Kinase Inhibitors, Adaptor Proteins, Signal Transducing, Wnt Proteins, beta Catenin
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