期刊
TRAFFIC
卷 11, 期 6, 页码 813-826出版社
WILEY
DOI: 10.1111/j.1600-0854.2010.01059.x
关键词
FGF2; membrane translocation; non-classical export; phosphorylation; RNAi screening; Tec kinase; unconventional protein secretion
类别
资金
- Landesstiftung Baden-Wurttemberg
- German Research Foundation [SFB 638, GRK 1188]
- European Science Foundation
- Federal Ministry of Education and Research of Germany (BMBF) [0313923]
- DFG
Fibroblast growth factor 2 (FGF2) is a potent mitogen that is exported from cells by an endoplasmic reticulum (ER)/Golgi-independent mechanism. Unconventional secretion of FGF2 occurs by direct translocation across plasma membranes, a process that depends on the phosphoinositide phosphatidylinositol 4,5-biphosphate (PI(4,5)P-2) at the inner leaflet as well as heparan sulfate proteoglycans at the outer leaflet of plasma membranes; however, additional core and regulatory components of the FGF2 export machinery have remained elusive. Here, using a highly effective RNAi screening approach, we discovered Tec kinase as a novel factor involved in unconventional secretion of FGF2. Tec kinase does not affect FGF2 secretion by an indirect mechanism, but rather forms a heterodimeric complex with FGF2 resulting in phosphorylation of FGF2 at tyrosine 82, a post-translational modification shown to be essential for FGF2 membrane translocation to cell surfaces. Our findings suggest a crucial role for Tec kinase in regulating FGF2 secretion under various physiological conditions and, therefore, provide a new perspective for the development of a novel class of antiangiogenic drugs targeting the formation of the FGF2/Tec complex.
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