Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 277, Issue 40, Pages 37382-37393Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M204491200
Keywords
-
Categories
Funding
- NCI NIH HHS [CA89828] Funding Source: Medline
- NIGMS NIH HHS [GM55586] Funding Source: Medline
Ask authors/readers for more resources
RhoA, in its active GTP-bound form, stimulates transcription through activation of the serum-response factor (SRF). We found that cGMP inhibited serum-induced Rho-GTP loading and transcriptional activation of SRF-dependent reporter genes in smooth muscle and glial cells in a cGMP-dependent protein kinase (G-kinase)-dependent fashion. Serum stimulation of the SRF target gene vinculin was also blocked by cGMP/G-kinase. G-kinase activation inhibited SRF-dependent transcription induced by upstream RhoA activators including Galpha(13) and p115RhoGEF, with Galpha(13)-induced Rho-GTP loading inhibited by G-kinase. G-kinase had no effect on the high activation levels of RhoA(63L) or the double mutant RhoA(63L,188A) but inhibited transcriptional activation by these two RhoA mutants to a similar extent, suggesting an effect downstream of RhoA and independent of RhoA Ser(188) phosphorylation. Constitutively active forms of the Rho effectors Rho kinase (ROK), PKN, and PRK-2 induced SRF-dependent transcription in a cell type-specific fashion with ROK being the most efficient; G-kinase inhibited transcription induced by all three effectors without affecting ROK catalytic activity. G-kinase had no effect on RhoA(63L)induced morphological changes in glial cells, suggesting distinct transcriptional and cytoskeletal effectors of RhoA. We conclude that G-kinase inhibits SRF-dependent transcription by interfering with RhoA signaling; G-kinase acts both upstream of RhoA, inhibiting serum- or Galpha(13)-induced Rho activation, and downstream of RhoA, inhibiting steps distal to the Rho targets ROK, PKN, and PRK-2.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available