Fibroblast growth factor-heparan sulfate interaction interface (FGF-HS interface) (FGF-HS interface)

The Fibroblast growth factor-heparan sulfate (FGF-HS) interaction interface is a critical regulatory site for the activation of FGF signaling pathways. FGFs are a family of growth factors that require heparan sulfate proteoglycans (HSPGs) as essential co-receptors to facilitate stable binding and dimerization of their cognate tyrosine kinase receptors (FGFRs) (Ornitz, 2000, BioEssays). This interaction interface involves specific basic amino acid residues on the FGF protein and negatively charged sulfate groups on the HS chains (Pellegrini, 2001, Curr Opin Struct Biol). By stabilizing the ternary FGF-HS-FGFR complex, this interface enables downstream signal transduction essential for cell proliferation, differentiation, and angiogenesis (Zhou et al., 2011, Med Res Rev). In pathological states, such as cancer, dysregulation of this interface can drive tumor growth and neovascularization (Galliher & Schiemann, 2006, Cancer Res). Consequently, this interface has become a therapeutic target for heparin mimetics and small molecules designed to disrupt FGF-HS binding, thereby inhibiting aberrant signaling in oncology and fibrotic diseases (Dredge et al., 2010, Br J Cancer). Additionally, small molecules and antibodies are being explored to specifically disrupt this interface to treat fibrotic and cardiovascular diseases. Because heparan sulfate is ubiquitous, achieving selectivity for the FGF-HS interface over other growth factor-HS interactions remains a significant pharmacological challenge.

Other names

FGF-heparin binding siteFGF-heparan sulfate proteoglycan complexFGF-HS binding domainFGF-HSPG interaction site

Competitive inhibition of the binding between fibroblast growth factors (FGFs) and heparan sulfate (HS) chains, which prevents the stabilization and dimerization of FGF receptors (FGFRs) required for signal activation (Pellegrini, 2001, Curr Opin Struct Biol).