Casein Kinase Iε Enhances the Binding of Dvl-1 to Frat-1 and Is Essential for Wnt-3a-induced Accumulation of β-Catenin*

By S. Hino, T. Michiue, Makoto Asashima, A. Kikuchi. Journal of Biological Chemistry, 2003

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We demonstrate that Dvl-1, casein kinase Iε (CKIε), 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 CKIε. Coexpression of Dvl-1 and Frat-1 caused accumulation of β-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-(Δ228–250), which lacks the amino acid region 228–250 from Dvl-1, and Frat-1 did not. Dvl-1, but not Dvl-1-(Δ228–250), acted synergistically with CKIε to activate Tcf-4. Depletion of CKIε 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 CKIε reduced the Wnt-3a-induced accumulation of β-catenin, although it did not affect the basal level of β-catenin. These results indicate that CKIε-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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/78f330bb5b32e4c81d4069712d2c7b5789fbc929

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Citations in the corpus

Casein Kinase Iε Modulates the Signaling Specificities of Dishevelled (2004, methodology): “Indeed, it has been shown that overexpression of CKIe enhances the interaction between Dvl and GBP/ Frat ( 20 , 27).”