FGF1 gene

The FGF1 gene (FGF1 stands for: Fibroblast Growth Factor 1) is a protein-coding gene located on chromosome 5q31.3. Several alternatively spliced variants encoding different isoforms have been described. An important paralog of this gene is FGF2.

The protein encoded by the FGF1 gene is a member of the fibroblast growth factor (FGF) family. FGF family members have broad mitogenic and cellular survival activity and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. The FGF1 protein acts as a modifier of endothelial cell migration and proliferation and as an angiogenic factor. In vitro, it acts as a mitogen for a large number of mesoderm and neuroectoderm cells and is therefore presumably involved in organogenesis.

The FGF1 protein plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Acts as a strong mitogen in vitro. Acts as a ligand for FGFR1 and various integrins. integrins. Binds to FGFR1 in the presence of heparin, leading to dimerization and activation of FGFR1 by sequential autophosphorylation at tyrosine residues that serve as docking sites for interacting proteins, resulting in activation of multiple signaling cascades.

Binds to the integrin ITGAV:ITGB3. Basically, integrins play a role in fibroblast growth factor (FGF) signaling by interacting with FGF receptors (FGFRs). FGF1 binds directly to the soluble integrin ITGAV:ITGB3 located on the cell surface. Antagonists against ITGAV:ITGB3 block this interaction. The binding to integrin, the subsequent formation of a ternary complex with integrin and FGFR1 and the recruitment of PTPN11 into the complex are essential for FGF1 signaling (Mori S et al. 2008; Yamaji S et al. 2010). Induces phosphorylation and activation of FGFR1, FRS2, MAPK3/ERK1, MAPK1/ERK2 and AKT1. Can trigger angiogenesis (Mori S et al. (2013)

1. Mori S et al. (2008) Direct binding of integrin alphavbeta3 to FGF1 plays a role in FGF1 signaling. J Biol Chem 283:18066-18075.
2. Mori S et al. (2013) A dominant-negative FGF1 mutant (the R50E mutant) suppresses tumorigenesis and angiogenesis. PLoS One 8:e57927.
3. Yamaji S et al. (2010) A novel fibroblast growth factor-1 (FGF1) mutant that acts as an FGF antagonist. PLoS One 5:e10273.