Expression and purification of intracrine human FGF11 and study on its FGFR-dependent biological activity

Expression and purification of intracrine human FGF11 and study on its FGFR-dependent biological activity
Lee, Kyeong Won; An, Young Jun; Lee, Janet; Jung, Ye-Eun; Ko, In Young; Jin, Jonghwa; Park, Ji Hoon; Lee, Won Kyu; Cha, Kiweon; Cha, Sun Shin; Lee, Jung Hyun; Yim, Hyung Soon
KIOST Author(s)
Lee, Kyeong Won(이경원)An, Young Jun(안영준)Lee, Jung Hyun(이정현)Yim, Hyung Soon(임형순)
Alternative Author(s)
이경원; 안영준; 이정현; 임형순
Publication Year
Fibroblast growth factor 11 (FGF11) is one of intracrine FGFs (iFGFs), which function within cells. Unlike canonical FGFs, FGF11 remains intracellularly and plays biological roles in FGF receptor (FGFR)-independent manner. Here, we established expression system and construction of recombinant FGF11 proteins in E. coli and investigated whether extracellular administration of FGF11 can activate cellular signaling. Human FGF11 has two isoforms, FGF11a and FGF11b depending on the presence of nuclear localization sequences (NLS) in N-terminus. Since two FGF11 isoforms are unstable, FGF11a-Mut with the substitution of 3 cysteine in NLS with serine and C-terminal truncated FGF11b-dC were prepared. The introduction of mutation in NLS improved the solubility of FGF11 prepared from E. coli. The exogenous addition of FGF11b and FGF11b-dC into BALB3T3 increased cell proliferation while FGF11a-Mut exerted no effect. FGF11b-dC showed higher activity of cell proliferation and FGFR signaling than FGF11b. The cell-proliferating activities by FGF11b and FGF11b-dC were blocked by FGFR1 inhibitor or competition using recombinant FGFR1, implying FGFR1-dependent extracellular activity of FGF11b. The analysis of circular dichroism provided the possibility that C-terminus of FGF11 has an alpha-helix structure, which may affect interaction with FGFR1. These results suggest that N-and C-terminus of recombinant FGF11 are involved in the activation of FGFR1. The study for a novel function and mechanism of FGF11 may provide important insight to develop useful ligands for FGFR regulation.
Bibliographic Citation
제18회 한국해양바이오학회 정기총회 및 학술발표회, pp.223, 2022
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