Casein kinase I phosphorylates the Armadillo protein and induces its degradation in Drosophila
Open Access
- 1 April 2002
- journal article
- research article
- Published by Springer Nature in The EMBO Journal
- Vol. 21 (7), 1733-1742
- https://doi.org/10.1093/emboj/21.7.1733
Abstract
Casein kinase I (CKI) was recently reported as a positive regulator of Wnt signaling in vertebrates and Caenorhabditis elegans. To elucidate the function of Drosophila CKI in the wingless (Wg) pathway, we have disrupted its function by double‐stranded RNA‐mediated interference (RNAi). While previous findings were mainly based on CKI overexpression, this is the first convincing loss‐of‐function analysis of CKI. Surprisingly, CKIα‐ or CKIϵ‐RNAi markedly elevated the Armadillo (Arm) protein levels in Drosophila Schneider S2R+ cells, without affecting its mRNA levels. Pulse–chase analysis showed that CKI‐RNAi stabilizes Arm protein. Moreover, Drosophila embryos injected with CKIα double‐stranded RNA showed a naked cuticle phenotype, which is associated with activation of Wg signaling. These results indicate that CKI functions as a negative regulator of Wg/Arm signaling. Overexpression of CKIα induced hyper‐phosphorylation of both Arm and Dishevelled in S2R+ cells and, conversely, CKIα‐RNAi reduced the amount of hyper‐modified forms. His‐tagged Arm was phosphorylated by CKIα in vitro on a set of serine and threonine residues that are also phosphorylated by Zeste‐white 3. Thus, we propose that CKI phosphorylates Arm and stimulates its degradation.Keywords
This publication has 40 references indexed in Scilit:
- Axin-dependent Phosphorylation of the Adenomatous Polyposis Coli Protein Mediated by Casein Kinase 1εJournal of Biological Chemistry, 2001
- Physiological regulation of β-catenin stability by Tcf3 and CK1ϵ The Journal of cell biology, 2001
- Synergistic Activation of the Wnt Signaling Pathway by Dvl and Casein Kinase IεJournal of Biological Chemistry, 2001
- Crystal Structure of Glycogen Synthase Kinase 3βCell, 2001
- Casein kinase I transduces Wnt signalsNature, 1999
- Adenomatous Polyposis Coli Tumor Suppressor Protein Has Signaling Activity in Xenopus laevis Embryos Resulting in the Induction of an Ectopic Dorsoanterior AxisThe Journal of cell biology, 1997
- The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3.Genes & Development, 1996
- Biological activity of soluble wingless protein in cultured Drosophila imaginal disc cellsNature, 1994
- wingless signaling acts through zeste-white 3, the drosophila homolog of glycogen synthase kinase-3, to regulate engrailed and establish cell fateCell, 1992
- Multisite phosphorylation of glycogen synthase from rabbit skeletal muscleFEBS Letters, 1982