Instability restricts signaling of multiple fibroblast growth factors

0445257 - ÚŽFG 2016 RIV CH eng J - Journal Article
Buchtová, Marcela - Chaloupková, R. - Zakrzewska, M. - Veselá, I. - Celá, Petra - Barathová, J. - Gudernová, I. - Zajíčková, R. - Trantírek, L. - Martin, J. - Kostas, M. - Otlewski, J. - Damborský, J. - Kozubík, Alois - Wiedlocha, A. - Krejčí, P.
Instability restricts signaling of multiple fibroblast growth factors.
Cellular and Molecular Life Sciences. Roč. 72, č. 12 (2015), s. 2445-2459. ISSN 1420-682X. E-ISSN 1420-9071
R&D Projects: GA ČR(CZ) GA14-31540S; GA ČR GBP302/12/G157
Institutional support: RVO:67985904 ; RVO:68081707
Keywords : fibroblast growth factor * FGF * unstable
Subject RIV: EA - Cell Biology
Impact factor: 5.694, year: 2015

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.
Permanent Link: http://hdl.handle.net/11104/0247598