title: Instability restricts signaling of multiple fibroblast growth factors.
abstract: 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.
authors: Department of Anatomy, Histology and Embryology, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic.
authors: Marcela
authors: M
authors: Buchtova
authors: Radka
authors: R
authors: Chaloupkova
authors: Malgorzata
authors: M
authors: Zakrzewska
authors: Iva
authors: I
authors: Vesela
authors: Petra
authors: P
authors: Cela
authors: Jana
authors: J
authors: Barathova
authors: Iva
authors: I
authors: Gudernova
authors: Renata
authors: R
authors: Zajickova
authors: Lukas
authors: L
authors: Trantirek
authors: Jorge
authors: J
authors: Martin
authors: Michal
authors: M
authors: Kostas
authors: Jacek
authors: J
authors: Otlewski
authors: Jiri
authors: J
authors: Damborsky
authors: Alois
authors: A
authors: Kozubik
authors: Antoni
authors: A
authors: Wiedlocha
authors: Pavel
authors: P
authors: Krejci
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002813:Chondrosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002942:Circular Dichroism; D005260:Female; D005346:Fibroblast Growth Factors / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D055550:Protein Stability; D051381:Rats; D015398:Signal Transduction; D013696:Temperature; D014407:Tumor Cells, Cultured
chemical_list: D050505:Mutant Proteins; D005346:Fibroblast Growth Factors