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

EMBO J. 2002 Apr 2;21(7):1733-42. doi: 10.1093/emboj/21.7.1733.


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, CKIalpha- or CKIepsilon-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 CKIalpha 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 CKIalpha induced hyper-phosphorylation of both Arm and Dishevelled in S2R+ cells and, conversely, CKIalpha-RNAi reduced the amount of hyper-modified forms. His-tagged Arm was phosphorylated by CKIalpha 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Armadillo Domain Proteins
  • Casein Kinases
  • Cell Line
  • DNA-Binding Proteins / metabolism
  • Dishevelled Proteins
  • Drosophila Proteins*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Insect Proteins / biosynthesis
  • Insect Proteins / metabolism*
  • Molecular Sequence Data
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism
  • RNA, Antisense
  • RNA, Small Interfering
  • Serine / metabolism
  • Signal Transduction*
  • Threonine / metabolism
  • Trans-Activators*
  • Transcription Factors
  • Wnt1 Protein


  • ARM protein, Drosophila
  • Adaptor Proteins, Signal Transducing
  • Armadillo Domain Proteins
  • DNA-Binding Proteins
  • Dishevelled Proteins
  • Drosophila Proteins
  • Insect Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • RNA, Antisense
  • RNA, Small Interfering
  • Trans-Activators
  • Transcription Factors
  • Wnt1 Protein
  • ci protein, Drosophila
  • dsh protein, Drosophila
  • wg protein, Drosophila
  • Threonine
  • Serine
  • Protein Kinases
  • Casein Kinases