Rho-kinase contributes to sustained RhoA activation through phosphorylation of p190A RhoGAP

Kazutaka Mori, Mutsuki Amano, Mikito Takefuji, Katsuhiro Kato, Yasuhiro Morita, Tomoki Nishioka, Yoshiharu Matsuura, Toyoaki Murohara, Kozo Kaibuchi

研究成果: Article査読

53 被引用数 (Scopus)

抄録

RhoA is transiently activated by specific extracellular signals such as endothelin-1 (ET-1) in vascular smooth muscle cells. RhoGAP negatively regulates RhoA activity: thus, RhoA becomes the GDP-bound inactive form afterward. Sustained activation of RhoA is induced with high doses of the extracellular signals and is implicated in certain diseases such as vasospasms. However, it remains largely unknown how prolonged activation of RhoA is induced. Here we show that Rho-kinase, an effector of RhoA, phosphorylated p190A RhoGAP at Ser1150 and attenuated p190A RhoGAP activity in COS7 cells. Binding of Rnd to p190A RhoGAP is thought to enhance its activation. Phosphorylation of p190A RhoGAP by Rho-kinase impaired Rnd binding. Stimulation of vascular smooth muscle cells with a high dose of ET-1 provoked sustained RhoA activation and p190A RhoGAP phosphorylation, both of which were prohibited by a Rho-kinase inhibitor. The phosphomimic mutation of p190A RhoGAP weakened Rnd binding and RhoGAP activities. Taken together, these results suggest that ET-1 induces Rhokinase activation and subsequent phosphorylation of p190A RhoGAP, leading to prolonged RhoA activation.

本文言語English
ページ(範囲)5067-5076
ページ数10
ジャーナルJournal of Biological Chemistry
284
8
DOI
出版ステータスPublished - 20-02-2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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