The small GTP-binding protein RhoA regulates c-Jun by a ROCK-JNK signaling axis
The small GTP-binding protein RhoA regulates c-Jun by a ROCK-JNK signaling axis
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DOI：
10.1016/s1097-2765(04)00153-4
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发表时间：
2004-04-09
期刊：
影响因子：
16
通讯作者：
Gutkind, JS
中科院分区：
文献类型：
--
作者：
Marinissen, MJ;Chiariello, M;Gutkind, JS
RhoA调节肌动蛋白细胞骨架和与细胞增殖相关的基因的表达。这包括c-fos和c-jun，它们是在正常和异常细胞生长中起关键作用的转录因子的AP 1家族的成员。而RhoA刺激c-fos SRE最近阐明的机制，这是依赖于肌动蛋白的转录，RhoA如何调节c-jun仍然知之甚少。我们发现RhoA通过ROCK刺激c-jun表达，但独立于ROCK促进肌动蛋白聚合的能力。相反，我们发现ROCK激活JNK，然后在与c-jun启动子结合时磷酸化c-Jun和ATF 2。因此，ROCK代表RhoA下游的信号发散点，因为它促进肌动蛋白重组和随后的c-fos SRE表达，而平行途径将ROCK连接到JNK，从而刺激c-jun表达。最终，这些通路在细胞核中会聚以调节AP 1活性。
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.