转化生长因子β诱导的RhoA和p160ROCK激活参与了对Cdc25A的抑制，从而导致细胞周期停滞。
TGF-beta-induced RhoA and p160ROCK activation is involved in the inhibition of Cdc25A with resultant cell-cycle arrest.
作者信息
Bhowmick Neil A, Ghiassi Mayshan, Aakre Mary, Brown Kimberly, Singh Vikas, Moses Harold L
机构信息
Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232-6838, USA.
出版信息
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15548-53. doi: 10.1073/pnas.2536483100. Epub 2003 Dec 1.
Abstract
The ability of the transforming growth factor beta (TGF-beta) signaling pathways to inhibit proliferation of most cells while stimulating proliferation of others remains a conundrum. In this article, we report that the absence of RhoA and p160ROCK activity in fibroblastic NIH 3T3 cells and its presence in epithelial NMuMG cells can at least partially explain the difference in the TGF-beta growth response. Further, evidence is presented for TGF-beta-stimulated p160ROCK translocation to the nucleus and inhibitory phosphorylation of the cyclin-dependent kinase-activating phosphatase, Cdc25A. The resultant suppression of Cdk2 activity contributes to G1/S inhibition in NMuMG cells. These data provide evidence that signaling through RhoA and p160ROCK is important in TGF-beta inhibition of cell proliferation and links signaling components for epithelial transdifferentiation with regulation of cell-cycle progression.
摘要
转化生长因子β（TGF-β）信号通路在抑制大多数细胞增殖的同时却刺激其他细胞增殖，这一现象仍然是个谜。在本文中，我们报告称，成纤维细胞系NIH 3T3细胞中缺乏RhoA和p160ROCK活性，而上皮细胞系NMuMG细胞中存在该活性，这至少可以部分解释TGF-β生长反应的差异。此外，有证据表明TGF-β刺激p160ROCK转位至细胞核，并对细胞周期蛋白依赖性激酶激活磷酸酶Cdc25A进行抑制性磷酸化。由此导致的Cdk2活性抑制促成了NMuMG细胞中的G1/S期抑制。这些数据证明，通过RhoA和p160ROCK进行的信号传导在TGF-β抑制细胞增殖过程中很重要，并将上皮转分化的信号成分与细胞周期进程的调节联系起来。
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