Fibroblast growth factor receptor 1-4 (FGFR1-4) with heparan sulfate proteoglycans (HSPGs) (FGFR1-4/HSPG)

The Fibroblast Growth Factor Receptor 1-4 (FGFR1-4) with heparan sulfate proteoglycans (HSPGs) as coreceptors forms a critical signaling apparatus on the cell surface. FGFRs are receptor tyrosine kinases that require the presence of HSPGs to stabilize the binding of fibroblast growth factor (FGF) ligands and promote receptor dimerization and trans-phosphorylation (PMID: 11336702). This complex regulates fundamental biological processes, including cell proliferation, survival, and migration, as well as specialized functions like bone growth and phosphate homeostasis (PMID: 25762554). Aberrant FGFR signaling, often driven by genetic alterations such as fusions or mutations, is implicated in numerous cancers, including intrahepatic cholangiocarcinoma and urothelial carcinoma (PMID: 31067451). Therapeutic strategies include small-molecule tyrosine kinase inhibitors (TKIs) like erdafitinib and pemigatinib, which block the intracellular kinase activity of the receptors. A notable clinical challenge is hyperphosphatemia, a class-wide side effect caused by the inhibition of FGFR1, which disrupts the FGF23-mediated regulation of phosphate levels in the kidneys (PMID: 29675221).

Other names

FGFR1FGFR2FGFR3FGFR4CD331CD332CD333CD334Heparan sulfate proteoglycan coreceptorsFGF receptor complex

Small molecule inhibitors typically bind to the intracellular tyrosine kinase domain of FGFR1-4, competing with ATP to prevent autophosphorylation and downstream signaling (PMID: 31067451). Monoclonal antibodies may target the extracellular domain to block ligand binding or receptor dimerization facilitated by heparan sulfate proteoglycans (PMID: 21399661).