論文

査読有り 国際誌
2018年7月26日

The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis.

Development (Cambridge, England)
  • Takashi Iezaki
  • Kazuya Fukasawa
  • Tetsuhiro Horie
  • Gyujin Park
  • Samuel Robinson
  • Michio Nakaya
  • Hiroyuki Fujita
  • Yuki Onishi
  • Kakeru Ozaki
  • Takashi Kanayama
  • Manami Hiraiwa
  • Yuka Kitaguchi
  • Katsuyuki Kaneda
  • Yukio Yoneda
  • Takeshi Takarada
  • X Edward Guo
  • Hitoshi Kurose
  • Eiichi Hinoi
  • 全て表示

145
14
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1242/dev.164004

Erk5 belongs to the mitogen-activated protein kinase (MAPK) family. Following its phosphorylation by Mek5, Erk5 modulates several signaling pathways in a number of cell types. In this study, we demonstrated that Erk5 inactivation in mesenchymal cells causes abnormalities in skeletal development by inducing Sox9, an important transcription factor of skeletogenesis. We further demonstrate that Erk5 directly phosphorylates and activates Smurf2 (a ubiquitin E3 ligase) at Thr249, which promotes the proteasomal degradation of Smad proteins and phosphorylates Smad1 at Ser206 in the linker region known to trigger its proteasomal degradation by Smurf1. Smads transcriptionally activated the expression of Sox9 in mesenchymal cells. Accordingly, removal of one Sox9 allele in mesenchymal cells from Erk5-deficient mice rescued some abnormalities of skeletogenesis. These findings highlight the importance of the Mek5-Erk5-Smurf-Smad-Sox9 axis in mammalian skeletogenesis.

リンク情報
DOI
https://doi.org/10.1242/dev.164004
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29986870
ID情報
  • DOI : 10.1242/dev.164004
  • ISSN : 0950-1991
  • PubMed ID : 29986870

エクスポート
BibTeX RIS