The small GTP-binding protein RhoA regulates c-Jun by a ROCK-JNK signaling axis

被引:191
作者
Marinissen, MJ
Chiariello, M
Tanos, T
Bernard, O
Narumiya, S
Gutkind, JS [1 ]
机构
[1] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA
[2] Univ Buenos Aires, Fac Ciencias Exactas, Buenos Aires, DF, Argentina
[3] CNR, Ist Endocrinol & Oncol Sperimentale, I-80131 Naples, Italy
[4] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia
[5] Kyoto Univ, Fac Med, Dept Pharmacol, Sakyo Ku, Kyoto 6068501, Japan
关键词
D O I
10.1016/S1097-2765(04)00153-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:29 / 41
页数:13
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