cGMP-Dependent Protein Kinase Phosphorylates and Inactivates RhoA

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...

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Published in:Biochemical and biophysical research communications 2001-01, Vol.280 (3), p.798-805
Main Authors: Sawada, Naoki, Itoh, Hiroshi, Yamashita, Jun, Doi, Kentaro, Inoue, Mayumi, Masatsugu, Ken, Fukunaga, Yasutomo, Sakaguchi, Satsuki, Sone, Masakatsu, Yamahara, Ken-ichi, Yurugi, Takami, Nakao, Kazuwa
Format: Article
Language:English
Subjects:
Actins - metabolism
Base Sequence
Biological Transport, Active
Cell Membrane - metabolism
cGMP
cGMP-dependent protein kinase
Cyclic GMP-Dependent Protein Kinases - genetics
Cyclic GMP-Dependent Protein Kinases - metabolism
Cytosol - metabolism
DNA Primers - genetics
HeLa Cells
Humans
Intracellular Signaling Peptides and Proteins
Lysophospholipids - pharmacology
membrane translocation
Mutation
Phosphorylation
Protein-Serine-Threonine Kinases - metabolism
rac1 GTP-Binding Protein - metabolism
Rho
rho-Associated Kinases
rhoA GTP-Binding Protein - antagonists & inhibitors
rhoA GTP-Binding Protein - chemistry
rhoA GTP-Binding Protein - genetics
rhoA GTP-Binding Protein - metabolism
Serine - chemistry
small GTP binding protein
stress fiber
Transfection
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2000.4194