Phosphorylation and interaction of myopodin by integrin-link kinase lead to suppression of cell growth and motility in prostate cancer cells.
Phosphorylation and interaction of myopodin by integrin-link kinase lead to suppression of cell growth and motility in prostate cancer cells.
复制标题
DOI：
10.1038/onc.2011.200
复制
发表时间：
2011-12-08
期刊：
影响因子：
8
通讯作者：
Luo, J-H
中科院分区：
文献类型：
--
作者：
Yu, Y-P;Luo, J-H
Myopodin 是一种肿瘤抑制基因，可抑制前列腺癌和尿路上皮癌的生长。然而，Myopodin 肿瘤抑制活性或导致 Myopodin 激活的信号传导机制仍不清楚。在本报告中，我们表明 myopodin 的 N 末端在体内和体外均与整合素连接激酶 (ILK) 结合。在 myopodin 的 N 末端区域发现了一个由 78 个氨基酸（氨基酸 82-157）组成的 ILK 相互作用基序。整合素 α7 诱导 ILK 依赖性激酶活性导致肌足蛋白在体内和体外磷酸化。敲除ILK可显着降低肌足蛋白介导的细胞生长和运动的抑制。缺乏 ILK 相互作用基序的 myopodin 突变体无法抑制 PC3 细胞的生长和运动。因此，这项研究展示了一条新颖且关键的信号通路，可导致肌足蛋白激活。
Myopodin is a tumor suppressor gene that suppresses growth of prostate and urothelial carcinomas. However, the mechanism of myopodin tumor suppressor activity or signaling that leads to activation of myopodin remains unclear. In this report, we showed that the N-terminus of myopodin binds integrin-linked kinase (ILK) both in vivo and in vitro. An ILK interaction motif of 78 amino acids (amino acids 82–157) was identified in the N-terminus region of myopodin. Induction of ILK dependent kinase activity by integrin α7 led to phosphorylation of myopodin both in vivo and in vitro. Knocking down ILK dramatically reduced the inhibition of cell growth and motility mediated by myopodin. A mutant of myopodin lacking the ILK interaction motif is inactive in suppressing the growth and motility of PC3 cells. As a result, this study showed a novel and critical signaling pathway that leads to activation of myopodin.
登录
查看更多内容
影响因子：
13.5
作者：
Apte, Udayan;Gkretsi, Vasiliki;Bowen, William C.;Mars, Wendy M.;Luo, Jian-Hua;Donthamsetty, Shashikiran;Orr, Ann;Monga, Satdarshan P. S.;Wu, Chuanyue;Michalopoulos, George K.
通讯作者：
Michalopoulos, George K.
影响因子：
13.5
作者：
Gkretsi, Vasiliki;Apte, Udayan;Mars, Wendy M.;Bowen, William C.;Luo, Jian-Hua;Yang, Yu;Yu, Yan P.;Orr, Ann;St-Arnaud, Rene;Dedhar, Shoukat;Kaestner, Klaus H.;Wu, Chuanyue;Michalopoulos, George K.
通讯作者：
Michalopoulos, George K.
影响因子：
4.8
作者：
Deng, JT;Van Lierop, JE;Walsh, MP
通讯作者：
Walsh, MP
影响因子：
6
作者：
Lin, F;Yu, YP;Luo, JH
通讯作者：
Luo, JH
DOI：
10.1073/pnas.0701999104
发表时间：
2007-04-17
影响因子：
11.1
作者：
Acconcia, Filippo;Barnes, Christopher J.;Kumar, Rakesh
通讯作者：
Kumar, Rakesh