Elsevier

Developmental Biology

Volume 235, Issue 2, 15 July 2001, Pages 388-396
Developmental Biology

Regular Article
The Casein Kinase I Family in Wnt Signaling

https://doi.org/10.1006/dbio.2001.0308Get rights and content
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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.

Keywords

Casein Kinase I
Wnt
Dishevelled
signal transduction

Cited by (0)

1

R.M.M. and J.M.P. contributed equally to this work.

2

To whom correspondence should be addressed. Fax: (214) 648-1196. E-mail: [email protected].