Zhang Yu, Li Xiang, Qi Jingjing, Wang Jialu, Liu Xingfeng, Zhang Haiwen, Lin Sheng-Cai, Meng Anming
Protein Science Laboratory of Ministry of Education, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
J Cell Sci. 2009 Jul 1;122(Pt 13):2197-207. doi: 10.1242/jcs.040659. Epub 2009 Jun 9.
The Rho-associated serine/threonine kinases Rock1 and Rock2 play important roles in cell contraction, adhesion, migration, proliferation and apoptosis. Here we report that Rock2 acts as a negative regulator of the TGFbeta signaling pathway. Mechanistically, Rock2 binds to and accelerates the lysosomal degradation of TGFbeta type I receptors internalized from the cell surface in mammalian cells. The inhibitory effect of Rock2 on TGFbeta signaling requires its kinase activity. In zebrafish embryos, injection of rock2a mRNA attenuates the expression of mesodermal markers during late blastulation and blocks the induction of mesoderm by ectopic Nodal signals. By contrast, overexpression of a dominant negative form of zebrafish rock2a, dnrock2a, has an opposite effect on mesoderm induction, suggesting that Rock2 proteins are endogenous inhibitors for mesoderm induction. Thus, our data have unraveled previously unidentified functions of Rock2, in controlling TGFbeta signaling as well as in regulating embryonic patterning.
Rho 相关丝氨酸/苏氨酸激酶 Rock1 和 Rock2 在细胞收缩、黏附、迁移、增殖和凋亡中发挥重要作用。在此我们报告，Rock2 作为转化生长因子β（TGFβ）信号通路的负调节因子。从机制上来说，Rock2 在哺乳动物细胞中与从细胞表面内化的 TGFβ I 型受体结合并加速其溶酶体降解。Rock2 对 TGFβ 信号的抑制作用需要其激酶活性。在斑马鱼胚胎中，注射 rock2a mRNA 会减弱囊胚晚期中胚层标记物的表达，并阻断异位 Nodal 信号诱导的中胚层形成。相比之下，斑马鱼 rock2a 的显性负性形式 dnrock2a 的过表达对中胚层诱导有相反的作用，这表明 Rock2 蛋白是中胚层诱导的内源性抑制剂。因此，我们的数据揭示了 Rock2 在控制 TGFβ 信号以及调节胚胎模式形成方面以前未被识别的功能。
