FGF2

FGF2, or fibroblast growth factor 2, is a member of the fibroblast growth factor family encoded by the FGF2 gene in humans. It exists as multiple protein isoforms produced by alternative translation initiation, including a low molecular weight cytoplasmic form (~18 kDa) and several higher molecular weight nuclear forms. Lacking a conventional signal peptide, FGF2 is secreted via a non-classical pathway and becomes active in the extracellular space after association with heparan sulfate proteoglycans.

FGF2 signals mainly through fibroblast growth factor receptors (FGFR1–FGFR4) in the presence of heparan sulfate. Receptor activation triggers downstream pathways such as RAS/MAPK, PI3K/AKT, and PLCγ, promoting proliferation, survival, migration, and differentiation. Some isoforms localize to the nucleus and can influence gene expression.

In development and physiology, FGF2 participates in angiogenesis, wound healing, embryonic development, and neurogenesis, including maintenance of neural progenitors and modulation of synaptic function. In cell culture, FGF2 supports the proliferation of neural stem cells and is used to maintain human embryonic stem cells and induced pluripotent stem cells in an undifferentiated state when combined with other factors.

Clinical relevance: dysregulated FGF2 signaling contributes to tumor angiogenesis and cancer progression, making FGFRs and FGF2 attractive targets for therapy. Beyond oncology, FGF2 is studied for regenerative medicine and tissue engineering, and its activity is modulated by extracellular matrix components and sulfation patterns of heparan sulfate.