4.4 Article

The casein kinase I family in Wnt signaling

期刊

DEVELOPMENTAL BIOLOGY
卷 235, 期 2, 页码 388-396

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/dbio.2001.0308

关键词

casein kinase I; Wnt; dishevelled; signal transduction

资金

  1. NICHD NIH HHS [F32 HD08609-01, R01-HD36001-01A1] Funding Source: Medline

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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 I epsilon (CKI epsilon) as a positive component of the canonical wnt/beta -catenin pathway, and necessity tests showed that CKIe is required in vertebrates to transduce Wnt signals. In addition to CKI epsilon, the CKI family includes several other isoforms (alpha, beta, gamma ,and delta) 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 cw 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 gamma, 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. (C) 2001 Academic Press.

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