Instability restricts signaling of multiple fibroblast growth factors

被引：51

作者：

Buchtova, Marcela ^{[1
,2
,3
]}

Chaloupkova, Radka ^{[4
,5
]}

Zakrzewska, Malgorzata ^{[6
]}

Vesela, Iva ^{[1
,3
]}

Cela, Petra ^{[2
,3
]}

Barathova, Jana ^{[7
]}

Gudernova, Iva ^{[7
]}

Zajickova, Renata ^{[2
]}

Trantirek, Lukas ^{[8
,9
]}

Martin, Jorge ^{[10
]}

Kostas, Michal ^{[11
]}

Otlewski, Jacek ^{[6
]}

Damborsky, Jiri ^{[4
,5
,12
]}

Kozubik, Alois ^{[3
,13
]}

Wiedlocha, Antoni ^{[14
,15
]}

Krejci, Pavel ^{[7
,12
,16
]}

机构：

[1] Univ Vet & Pharmaceut Sci, Dept Anat Histol & Embryol, Brno, Czech Republic

[2] Acad Sci Czech Republ, Inst Anim Physiol & Genet, Brno, Czech Republic

[3] Masaryk Univ, Dept Expt Biol, Brno 62500, Czech Republic

[4] Masaryk Univ, Dept Expt Biol, Loschmidt Labs, Brno 62500, Czech Republic

[5] Masaryk Univ, Res Ctr Tox Cpds Environm RECETOX, Brno 62500, Czech Republic

[6] Univ Wroclaw, Dept Prot Engn, PL-50138 Wroclaw, Poland

[7] Masaryk Univ, Fac Med, Dept Biol, Brno 62500, Czech Republic

[8] Masaryk Univ, Cent European Inst Technol, Brno 62500, Czech Republic

[9] Univ Utrecht, Bijvoet Ctr Biomol Res, Utrecht, Netherlands

[10] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[11] Univ Wroclaw, Dept Prot Biotechnol, PL-50138 Wroclaw, Poland

[12] St Annes Univ Hosp, Int Clin Res Ctr, Brno, Czech Republic

[13] Acad Sci Czech Republ, Inst Biophys, Dept Cytokinet, CS-61265 Brno, Czech Republic

[14] Univ Oslo, Ctr Canc Biomed, Oslo, Norway

[15] Oslo Univ Hosp, Inst Canc Res, Dept Biochem, Oslo, Norway

[16] Univ Calif Los Angeles, David Geffen Sch Med, Dept Orthopaed Surg, Los Angeles, CA 90095 USA

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2015年 / 72卷 / 12期

关键词：

Fibroblast growth factor; FGF; Unstable; Proteoglycan; Regulation; RECEPTOR SPECIFICITY; FACTOR FAMILY; PROTEIN; PROLIFERATION; STABILITY; BINDING; FIBROBLAST-GROWTH-FACTOR-19; DIFFERENTIATION; POLYANIONS; AFFINITY;

D O I：

10.1007/s00018-015-1856-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2445 / 2459

页数：15

共 46 条

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