cGMP-dependent protein kinase phosphorylates and inactivates RhoA

N. Sawada, Hiroshi Itoh, J. Yamashita, K. Doi, M. Inoue, K. Masatsugu, Y. Fukunaga, S. Sakaguchi, Masakatsu Sone, K. I. Yamahara, T. Yurugi, K. Nakao

Research output: Contribution to journalArticle

181 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
Externally publishedYes

Fingerprint

Cyclic GMP-Dependent Protein Kinases
Stress Fibers
rhoA GTP-Binding Protein
rho-Associated Kinases
Monomeric GTP-Binding Proteins
Fibers
Cyclic AMP-Dependent Protein Kinases
HeLa Cells
Blood Vessels
Actins
Substitution reactions
Membranes
Growth

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

cGMP-dependent protein kinase phosphorylates and inactivates RhoA. / Sawada, N.; Itoh, Hiroshi; Yamashita, J.; Doi, K.; Inoue, M.; Masatsugu, K.; Fukunaga, Y.; Sakaguchi, S.; Sone, Masakatsu; Yamahara, K. I.; Yurugi, T.; Nakao, K.

In: Biochemical and Biophysical Research Communications, Vol. 280, No. 3, 2001, p. 798-805.

Research output: Contribution to journalArticle

Sawada, N, Itoh, H, Yamashita, J, Doi, K, Inoue, M, Masatsugu, K, Fukunaga, Y, Sakaguchi, S, Sone, M, Yamahara, KI, Yurugi, T & Nakao, K 2001, 'cGMP-dependent protein kinase phosphorylates and inactivates RhoA', Biochemical and Biophysical Research Communications, vol. 280, no. 3, pp. 798-805. https://doi.org/10.1006/bbrc.2000.4194
Sawada, N. ; Itoh, Hiroshi ; Yamashita, J. ; Doi, K. ; Inoue, M. ; Masatsugu, K. ; Fukunaga, Y. ; Sakaguchi, S. ; Sone, Masakatsu ; Yamahara, K. I. ; Yurugi, T. ; Nakao, K. / cGMP-dependent protein kinase phosphorylates and inactivates RhoA. In: Biochemical and Biophysical Research Communications. 2001 ; Vol. 280, No. 3. pp. 798-805.
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AU - Yurugi, T.

AU - Nakao, K.

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