Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is essential for Wnt-3a-induced accumulation of beta-catenin.
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Hino S, Michiue T, Asashima M, Kikuchi A
Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is essential for Wnt-3a-induced accumulation of beta-catenin.
J Biol Chem. 2003 Apr 18;278(16):14066-73. Epub 2003 Jan 28.
- PubMed ID
- 12556519 [ View in PubMed]
- Abstract
We demonstrate that Dvl-1, casein kinase I epsilon (CKI epsilon), and Frat-1 activate the Wnt signaling pathway cooperatively. The amino acid region 228-250 of Dvl-1 was necessary for its binding to Frat-1, and the interaction of Dvl-1 with Frat-1 was enhanced by CKI epsilon. Coexpression of Dvl-1 and Frat-1 caused accumulation of beta-catenin synergistically in L cells. Both proteins also activated the transcriptional activity of T-cell factor-4 (Tcf-4) synergistically in human embryonic kidney 293 cells, but coexpression of Dvl-1-(Delta 228-250), which lacks the amino acid region 228-250 from Dvl-1, and Frat-1 did not. Dvl-1, but not Dvl-1-(Delta 228-250), acted synergistically with CKI epsilon to activate Tcf-4. Depletion of CKI epsilon by double-stranded RNA interference in HeLa S3 cells led to the inhibition of Wnt-3a-induced phosphorylation of Dvl and the binding of Dvl-1 to Frat-1. Furthermore, depletion of CKI epsilon reduced the Wnt-3a-induced accumulation of beta-catenin, although it did not affect the basal level of beta-catenin. These results indicate that CKI epsilon-dependent phosphorylation of Dvl enhances the formation of a complex of Dvl-1 with Frat-1 and that this complex leads to the activation of the Wnt signaling pathway.