期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 21, 期 2, 页码 180-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.2752
关键词
-
资金
- G. Harold and Leila Y. Mathers Charitable Foundation
- US National Institutes of Health [DK070950]
FGFR2-expressing human cancer cells with low concentrations of the adaptor protein Grb2 show high prevalence for metastatic outcome. In nonstimulated cells, the SH3 domain (and not the SH2 domains) of Plc gamma 1 directly competes for a binding site at the very C terminus of FGFR2 with the C-terminal SH3 domain of Grb2. Reduction of Grb2 concentration permits Plc gamma 1 access to the receptor. Recruitment of Plc gamma 1 in this way is sufficient to upregulate phospholipase activity. This results in elevated phosphatidylinositol 4,5-bisphosphate turnover and intracellular calcium levels, thus leading to increased cell motility and promotion of cell-invasive behavior in the absence of extracellular receptor stimulation. Therefore, metastatic outcome can be dictated by the constitutive competition between Grb2 and Plc gamma 1 for the phosphorylation-independent binding site on FGFR2.
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