TY - JOUR
T1 - The casein kinase I family in Wnt signaling
AU - McKay, Renée M.
AU - Peters, John M.
AU - Graff, Jonathan M.
N1 - Funding Information:
We thank Takahisa Furukawa, Jin Jiang, Peter Klein, Mark Henke-meyer, Eric Olson, Luis Parada, and members of the Graff lab for helpful discussions. We thank Karl Willert for thoughtful comments as well as generously providing anti-Dvl1 polyclonal antibody and the C57MG, EL, and EL-Wnt3a cell lines. We thank M. Cobb for BCKIα and BCKIβ, F. Constantini for Axin, P. Klein for Xaxin, J. Kusuda for HCKIγ2 and HCKIγ3, and S. Sokol for Dsh and Xdd1. We thank Li Meng for technical assistance. R.M.M. is supported by NICHD (F32 HD08609-01). This work was supported by awards from the NIH (RO1-HD36001-01A1 from NICHD) and the March of Dimes (to J.M.G.). J.M.G. is a Charles E. Culpeper Medical Scholar and receives support from the Rockefeller Brothers Fund.
PY - 2001/7/15
Y1 - 2001/7/15
N2 - 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.
AB - 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.
KW - Casein kinase I
KW - Dishevelled
KW - Signal transduction
KW - Wnt
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U2 - 10.1006/dbio.2001.0308
DO - 10.1006/dbio.2001.0308
M3 - Article
C2 - 11437445
AN - SCOPUS:0035879301
SN - 0012-1606
VL - 235
SP - 388
EP - 396
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -