Casein kinase I phosphorylates the Armadillo protein and induces its degradation in Drosophila

Shin Ichi Yanagawa, Yukihiro Matsuda, Jong Seo Lee, Hiroko Matsubayashi, Sonoka Sese, Tatsuhiko Kadowaki, Akinori Ishimoto

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159 Citations (Scopus)

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 hyperphosphorylation 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.

Original languageEnglish
Pages (from-to)1733-1742
Number of pages10
JournalEMBO Journal
Volume21
Issue number7
DOIs
Publication statusPublished - 2 Apr 2002
Externally publishedYes

Keywords

  • Armadillo
  • Casein kinase I
  • Proteasome
  • RNAi
  • Wnt

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