The casein kinase I family in Wnt signaling

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

The canonical Wnt-signaling pathway is critical for many aspects of development, and mutations in components of the Wnt pathway are carcinogenic. Recently, sufficiency tests identified casein kinase Iε (CKIε) as a positive component of the canonical Wnt/β-catenin pathway, and necessity tests showed that CKIε is required in vertebrates to transduce Wnt signals. In addition to CKIε, the CKI family includes several other isoforms (α, β, γ, and δ) and their role in Wnt sufficiency tests had not yet been clarified. However, in Caenorhabditis elegans studies, loss-of-function of a CKI isoform most similar to α produced the mom phenotype, indicative of loss-of-Wnt signaling. In this report, we examine the ability of the various CKI isoforms to activate Wnt signaling and find that all the wild-type CKI isoforms do so. Dishevelled (Dsh), another positive component of the Wnt pathway, becomes phosphorylated in response to Wnt signals. All the CKI isoforms, with the exception of γ, increase the phosphorylation of Dsh in vivo. In addition, CKI directly phosphorylates Dsh in vitro. Finally, we find that CKI is required in vivo for the Wnt-dependent phosphorylation of Dsh. These studies advance our understanding of the mechanism of Wnt action and suggest that more than one CKI isoform is capable of transducing Wnt signals in vivo.

Original languageEnglish (US)
Pages (from-to)388-396
Number of pages9
JournalDevelopmental Biology
Volume235
Issue number2
DOIs
Publication statusPublished - Jul 15 2001

    Fingerprint

Keywords

  • Casein kinase I
  • Dishevelled
  • Signal transduction
  • Wnt

ASJC Scopus subject areas

  • Developmental Biology

Cite this