Affiliation:
1. Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-Ku, Kyoto 606-85071
2. Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-Ku, Tokyo 113-00332, Japan
Abstract
ABSTRACT
Regulation of Armadillo (Arm) protein levels through ubiquitin-mediated degradation plays a central role in the Wingless (Wg) signaling. Although zeste-white3 (Zw3)-mediated Arm phosphorylation has been implicated in its degradation, we have recently shown that casein kinase Iα (CKIα) also phosphorylates Arm and induces its degradation. However, it remains unclear how CKIα and Zw3, as well as other components of the Arm degradation complex, regulate Arm phosphorylation in response to Wg. In particular, whether Wg signaling suppresses CKIα- or Zw3-mediated Arm phosphorylaytion in vivo is unknown. To clarify these issues, we performed a series of RNA interference (RNAi)-based analyses in
Drosophila
S2R+ cells by using antibodies that specifically recognize Arm phosphorylated at different serine residues. These analyses revealed that Arm phosphorylation at serine-56 and at threonine-52, serine-48, and serine-44, is mediated by CKIα and Zw3, respectively, and that Zw3-directed Arm phosphorylation requires CKIα-mediated priming phosphorylation. Daxin stimulates Zw3- but not CKIα-mediated Arm phosphorylation. Wg suppresses Zw3- but not CKIα-mediated Arm phosphorylation, indicating that a vital regulatory step in Wg signaling is Zw3-mediated Arm phosphorylation. In addition, further RNAi-based analyses of the other aspects of the Wg pathway clarified that Wg-induced Dishevelled phosphoylation is due to CKIα and that presenilin and protein kinase A play little part in the regulation of Arm protein levels in
Drosophila
tissue culture cells.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
48 articles.
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