Design of a thrombin resistant human acidic fibroblast growth factor (hFGF1) variant that exhibits enhanced cell proliferation activity

Characterization of the structural forces governing the reversibility of the thermal unfolding of the human acidic fibroblast growth factor

“…1 ). We recently demonstrated that a charge reversal mutation (R136E) in the heparin-binding pocket (HBP) marginally decreases the heparin-binding affinity but enhances the cell proliferation activity of hFGF1 19 . hFGF1 is known to be inherently unstable molecule at temperatures just above the physiological temperature 20 .…”

“…hFGF1 is known to be inherently unstable molecule at temperatures just above the physiological temperature 20 . It is believed that the instability of hFGF1 largely stems from the charge repulsions between the closely placed positively charged residues in the HBP 19 . In this context, introduction of a negative charge in the HBP is postulated to provide a counter-ion effect and consequently stabilize hFGF1.…”

“…Far-UV CD measurements of wtFGF1 and hFGF1 variants were performed on a JASCO-1500 spectropolarimeter using a quartz cell of 1 mm path length. Each spectrum was recorded as an average of 3 scans and the wavelength range used was from 190 to 250 nm 19 , 20 . The concentration of the protein used was 30–35 μM in 10 mM sodium phosphate buffer (pH 7.2) containing 100 mM NaCl at 25 °C.…”

“…Human acidic fibroblast growth factor (hFGF1) is a ~ 16 kDa protein that aids in the regulation of key cellular processes such as cell proliferation, angiogenesis, tumor metastasis, and wound healing 19 – 23 . hFGF1 has a low half -life in vivo 24 .…”

Non-Mitogenic Fibroblast Growth Factor 1 Enhanced Angiogenesis Following Ischemic Stroke by Regulating the Sphingosine-1-Phosphate 1 Pathway

“…Fibroblast growth factor 1 (FGF1) is a member of the FGF family and regulates various cellular processes such as angiogenesis, cell migration, cell differentiation, wound healing, and tube formation via binding to FGF receptors and heparin sulfate proteoglycans (Cheng et al, 2011;Wu et al, 2017;Kerr et al, 2019). However, the mitogenic activity of FGF1 is known to contribute to metastasis and tumorigenesis (Cronauer et al, 2003;Li et al, 2007).…”