The small GTP-binding protein RhoA regulates c-Jun by a ROCK-JNK signaling axis
- Author(s)
- Marinissen, MJ; Chiariello, M; Tanos, T; Bernard, O; Narumiya, S; Gutkind, JS;
- Details
- Publication Year 2004-04-09,Volume 14,Issue #1,Page 29-41
- Journal Title
- MOLECULAR CELL
- Publication Type
- Journal Article
- Abstract
- RhoA regulates the actin cytoskeleton and the expression of genes associated with cell proliferation. This includes c-fos and c-jun, which are members of the AP1 family of transcription factors that play a key role in normal and aberrant cell growth. Whereas RhoA stimulates the c-fos SRE by a recently elucidated mechanism that is dependent on actin treadmilling, how RhoA regulates c-jun is still poorly understood. We found that RhoA stimulates c-jun expression through ROCK, but independently from the ability of ROCK to promote actin polymerization. Instead, we found that ROCK activates JNK, which then phosphorylates c-Jun and ATF2 when bound to the c-jun promoter. Thus, ROCK represents a point of signal divergence downstream from RhoA, as it promotes actin reorganization and the consequent expression from the c-fos SRE, while a parallel pathway connects ROCK to JNK, thereby stimulating c-jun expression. Ultimately, these pathways converge in the nucleus to regulate AP1 activity.
- Publisher
- CELL PRESS
- Keywords
- SERUM RESPONSE FACTOR; N-TERMINAL KINASE; ACTIN DYNAMICS; LIM-KINASE; ACTIVATION; TRANSFORMATION; PROMOTER; PATHWAY; GTPASES; SRF
- Publisher's Version
- https://doi.org/10.1016/S1097-2765(04)00153-4
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2004-04-09 12:00:00