期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 72, 期 12, 页码 2445-2459出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-015-1856-8
关键词
Fibroblast growth factor; FGF; Unstable; Proteoglycan; Regulation
资金
- Ministry of Education, Youth and Sports of the Czech Republic [KONTAKT LH12004, CZ.1.07/2.3.00/30.0053, LO1214]
- Grant Agency of Masaryk University [0071-2013]
- Czech Science Foundation [14-31540S, P207/12/0775, GBP302/12/G157]
- European Regional Development Fund (FNUSA-ICRC) [CZ.1.05/1.1.00/02.0123]
- European Union (ICRC-ERA-HumanBridge) [316345]
- Netherlands Organization for Scientific Research [700.59.426]
- Polish National Science Centre (NCN) [2011/02/A/NZ1/00066]
Fibroblast growth factors (FGFs) deliver extracellular signals that govern many developmental and regenerative processes, but the mechanisms regulating FGF signaling remain incompletely understood. Here, we explored the relationship between intrinsic stability of FGF proteins and their biological activity for all 18 members of the FGF family. We report that FGF1, FGF3, FGF4, FGF6, FGF8, FGF9, FGF10, FGF16, FGF17, FGF18, FGF20, and FGF22 exist as unstable proteins, which are rapidly degraded in cell cultivation media. Biological activity of FGF1, FGF3, FGF4, FGF6, FGF8, FGF10, FGF16, FGF17, and FGF20 is limited by their instability, manifesting as failure to activate FGF receptor signal transduction over long periods of time, and influence specific cell behavior in vitro and in vivo. Stabilization via exogenous heparin binding, introduction of stabilizing mutations or lowering the cell cultivation temperature rescues signaling of unstable FGFs. Thus, the intrinsic ligand instability is an important elementary level of regulation in the FGF signaling system.
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