論文

査読有り
2014年9月

Hipk2 and PP1c Cooperate to Maintain Dvl Protein Levels Required for Wnt Signal Transduction

CELL REPORTS
  • Nobuyuki Shimizu
  • ,
  • Shizuka Ishitani
  • ,
  • Atsushi Sato
  • ,
  • Hiroshi Shibuya
  • ,
  • Tohru Ishitani

8
5
開始ページ
1391
終了ページ
1404
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.celrep.2014.07.040
出版者・発行元
CELL PRESS

The phosphoprotein Dishevelled (Dvl) is a common essential component of Wnt/beta-catenin and Wnt/planar cell polarity (PCP) signaling pathways. However, the regulation and significance of Dvl phosphorylation are not fully understood. Here, we show that homeodomain-interacting protein kinase 2 (Hipk2) facilitates protein phosphatase 1 catalytic subunit (PP1c)-mediated dephosphorylation of Dvl via its C-terminal domain and that this dephosphorylation blocks ubiquitination and consequent degradation mediated by the E3 ubiquitin ligase Itch, which targets the phosphorylated form of Dvl proteins. Inhibition of Hipk2 or PP1c function reduces Dvl protein levels and suppresses Wnt/beta-catenin and Wnt/PCP pathway-dependent events in mammalian cells and zebrafish embryos, suggesting that Hipk2 and PP1c are essential for maintaining Dvl protein levels that are sufficient to activate Wnt signaling. We also show that Wnt-3a, a Wnt/beta-catenin ligand, induces dissociation of the Dvl-Hipk2-PP1c complex and Dvl degradation under high-cell-density conditions. This regulation may be a negative feedback mechanism that fine-tunes Wnt/beta-catenin signaling.

Web of Science ® 被引用回数 : 14

リンク情報
DOI
https://doi.org/10.1016/j.celrep.2014.07.040
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25159144
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000341574800017&DestApp=WOS_CPL

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