期刊
MOLECULAR CELL
卷 35, 期 1, 页码 11-25出版社
CELL PRESS
DOI: 10.1016/j.molcel.2009.06.013
关键词
-
资金
- University of Texas
- National Cancer Institute [5801 CA109035]
- MOST of China [200908918703]
Activated Ras has been found in many types of cancer. However, the mechanism underlying Ras-promoted tumor metastasis remains unclear. We demonstrate here that activated Ras induces tyrosine dephosphorylation and inhibition of FAK mediated by the Ras downstream Fgd1-Cdc42-PAK1-MEK-ERK signaling cascade. ERK phosphorylates FAK S910 and recruits PIN1 and PTP-PEST, which colocalize with FAK at the lamellipodia of migrating cells. PIN1 binding and prolyl isomerization of FAK cause PTP-PEST to interact with and dephosphorylate FAK Y397. Inhibition of FAK mediated by this signal relay promotes Ras-induced cell migration, invasion, and metastasis. These findings uncover the importance of sequential modification of FAK-by serine phosphorylation,isomerization, and tyrosine dephosphorylation-in the regulation of FAK activity and, thereby, in Ras-related tumor metastasis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据