caa a22 4500 606175504 CHVBK 20210128100743.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s00018-015-1856-8 doi (NATIONALLICENCE)springer-10.1007/s00018-015-1856-8 Instability restricts signaling of multiple fibroblast growth factors [Elektronische Daten] [Marcela Buchtova, Radka Chaloupkova, Malgorzata Zakrzewska, Iva Vesela, Petra Cela, Jana Barathova, Iva Gudernova, Renata Zajickova, Lukas Trantirek, Jorge Martin, Michal Kostas, Jacek Otlewski, Jiri Damborsky, Alois Kozubik, Antoni Wiedlocha, Pavel Krejci] 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. Springer Basel, 2015 Fibroblast growth factor nationallicence FGF nationallicence Unstable nationallicence Proteoglycan nationallicence Regulation nationallicence Buchtova Marcela Department of Anatomy, Histology and Embryology, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic aut Chaloupkova Radka Loschmidt Laboratories, Department of Experimental Biology and Research Centre for Toxic Compounds in the Environment RECETOX, Masaryk University, Brno, Czech Republic aut Zakrzewska Malgorzata Department of Protein Engineering, University of Wroclaw, Wroclaw, Poland aut Vesela Iva Department of Anatomy, Histology and Embryology, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic aut Cela Petra Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Brno, Czech Republic aut Barathova Jana Department of Biology, Faculty of Medicine, Masaryk University, Room A3/246, Kamenice 5, 625 00, Brno, Czech Republic aut Gudernova Iva Department of Biology, Faculty of Medicine, Masaryk University, Room A3/246, Kamenice 5, 625 00, Brno, Czech Republic aut Zajickova Renata Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Brno, Czech Republic aut Trantirek Lukas Central European Institute of Technology, Masaryk University, Brno, Czech Republic aut Martin Jorge Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA aut Kostas Michal Department of Protein Biotechnology, University of Wroclaw, Wroclaw, Poland aut Otlewski Jacek Department of Protein Engineering, University of Wroclaw, Wroclaw, Poland aut Damborsky Jiri Loschmidt Laboratories, Department of Experimental Biology and Research Centre for Toxic Compounds in the Environment RECETOX, Masaryk University, Brno, Czech Republic aut Kozubik Alois Department of Experimental Biology, Masaryk University, Brno, Czech Republic aut Wiedlocha Antoni Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway aut Krejci Pavel Department of Biology, Faculty of Medicine, Masaryk University, Room A3/246, Kamenice 5, 625 00, Brno, Czech Republic aut Cellular and Molecular Life Sciences Springer Basel 72/12(2015-06-01), 2445-2459 1420-682X 72:12<2445 2015 72 18 https://doi.org/10.1007/s00018-015-1856-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1856-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Buchtova Marcela Department of Anatomy, Histology and Embryology, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic aut NATIONALLICENCE 700 1- Chaloupkova Radka Loschmidt Laboratories, Department of Experimental Biology and Research Centre for Toxic Compounds in the Environment RECETOX, Masaryk University, Brno, Czech Republic aut NATIONALLICENCE 700 1- Zakrzewska Malgorzata Department of Protein Engineering, University of Wroclaw, Wroclaw, Poland aut NATIONALLICENCE 700 1- Vesela Iva Department of Anatomy, Histology and Embryology, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic aut NATIONALLICENCE 700 1- Cela Petra Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Brno, Czech Republic aut NATIONALLICENCE 700 1- Barathova Jana Department of Biology, Faculty of Medicine, Masaryk University, Room A3/246, Kamenice 5, 625 00, Brno, Czech Republic aut NATIONALLICENCE 700 1- Gudernova Iva Department of Biology, Faculty of Medicine, Masaryk University, Room A3/246, Kamenice 5, 625 00, Brno, Czech Republic aut NATIONALLICENCE 700 1- Zajickova Renata Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Brno, Czech Republic aut NATIONALLICENCE 700 1- Trantirek Lukas Central European Institute of Technology, Masaryk University, Brno, Czech Republic aut NATIONALLICENCE 700 1- Martin Jorge Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Kostas Michal Department of Protein Biotechnology, University of Wroclaw, Wroclaw, Poland aut NATIONALLICENCE 700 1- Otlewski Jacek Department of Protein Engineering, University of Wroclaw, Wroclaw, Poland aut NATIONALLICENCE 700 1- Damborsky Jiri Loschmidt Laboratories, Department of Experimental Biology and Research Centre for Toxic Compounds in the Environment RECETOX, Masaryk University, Brno, Czech Republic aut NATIONALLICENCE 700 1- Kozubik Alois Department of Experimental Biology, Masaryk University, Brno, Czech Republic aut NATIONALLICENCE 700 1- Wiedlocha Antoni Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway aut NATIONALLICENCE 700 1- Krejci Pavel Department of Biology, Faculty of Medicine, Masaryk University, Room A3/246, Kamenice 5, 625 00, Brno, Czech Republic aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/12(2015-06-01), 2445-2459 1420-682X 72:12<2445 2015 72 18