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Open AccessArticle

Low Stability of Integrin-Binding Deficient Mutant of FGF1 Restricts Its Biological Activity

1
Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland
2
Department of Protein Biotechnology, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Cells 2019, 8(8), 899; https://doi.org/10.3390/cells8080899
Received: 19 July 2019 / Revised: 9 August 2019 / Accepted: 14 August 2019 / Published: 15 August 2019
(This article belongs to the Section Cell Signaling and Regulated Cell Death)
Fibroblast growth factor 1 (FGF1) has been shown to interact with integrin αvβ3 through a specific binding site, involving Arg35 residue. The FGF1 mutant (R35E) with impaired integrin binding was found to be defective in its proliferative response, although it was still able to interact with FGF receptors (FGFR) and heparin and induce the activation of downstream signaling pathways. Here, we demonstrate that the lack of mitogenic potential of R35E mutant is directly caused by its decreased thermodynamic stability and susceptibility to proteolytic degradation. Introduction of three stabilizing mutations into R35E variant compensated the effect of destabilizing R35E mutation and restored the proliferation potential of FGF1. Moreover, the stabilized R35E variant regained both anti-apoptotic and wound healing activities, while remaining defective in binding to integrin αvβ3. Our results suggest that the thermodynamic stability and resistance to degradation, rather than the interaction with integrin are required for mitogenic response of FGF1. View Full-Text
Keywords: fibroblast growth factor 1; integrin αvβ3; protein stability; proteolytic degradation; mitogenic activity; protein-protein interaction; anti-apoptotic activity fibroblast growth factor 1; integrin αvβ3; protein stability; proteolytic degradation; mitogenic activity; protein-protein interaction; anti-apoptotic activity
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Szlachcic, A.; Sochacka, M.; Czyrek, A.; Opalinski, L.; Krowarsch, D.; Otlewski, J.; Zakrzewska, M. Low Stability of Integrin-Binding Deficient Mutant of FGF1 Restricts Its Biological Activity. Cells 2019, 8, 899.

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