cGMP-dependent protein kinase phosphorylates and inactivates RhoA

Naoki Sawada, Hiroshi Itoh, Jun Yamashita, Kentaro Doi, Mayumi Inoue, Ken Masatsugu, Yasutomo Fukunaga, Satsuki Sakaguchi, Masakatsu Sone, Ken ichi Yamahara, Takami Yurugi, Kazuwa Nakao

Research output: Contribution to journalArticle

186 Citations (Scopus)

Abstract

Small GTPase Rho and cGMP/cGMP-dependent protein kinase (cGK) pathways exert opposing effects in specific systems such as vascular contraction and growth. However, the direct interaction between these pathways has remained elusive. We demonstrate that cGK phosphorylates RhoA in vitro at Ser188, the same residue phosphorylated by cAMP-dependent protein kinase. In HeLa cells transfected with constitutively active cGK (C-cGK), stress fiber formation induced by lysophosphatidic acid or V14RhoA was blocked. By contrast, C-cGK failed to inhibit stress fiber formation in cells transfected with mutant RhoA with substitution of Ser188 to Ala. C-cGK did not affect actin reorganization induced by Rac1 or Rho-associated kinase, one of the effectors for RhoA. Furthermore, C-cGK expression inhibited the membrane translocation of RhoA. Collectively, our findings suggest that cGK phosphorylates RhoA at Ser188 and inactivates RhoA signaling. The physiological relevance of the direct interaction between RhoA and cGK awaits further investigation.

Original languageEnglish
Pages (from-to)798-805
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume280
Issue number3
DOIs
Publication statusPublished - 2001 Jan 1
Externally publishedYes

Keywords

  • Membrane translocation
  • Rho
  • Small GTP binding protein
  • Stress fiber
  • cGMP
  • cGMP-dependent protein kinase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Sawada, N., Itoh, H., Yamashita, J., Doi, K., Inoue, M., Masatsugu, K., Fukunaga, Y., Sakaguchi, S., Sone, M., Yamahara, K. I., Yurugi, T., & Nakao, K. (2001). cGMP-dependent protein kinase phosphorylates and inactivates RhoA. Biochemical and Biophysical Research Communications, 280(3), 798-805. https://doi.org/10.1006/bbrc.2000.4194