Fibroblast growth factor receptor–fibroblast growth factor 23 complex (FGFR–FGF23 complex)

The Fibroblast growth factor receptor–fibroblast growth factor 23 complex is a tripartite signaling assembly comprising an FGFR (typically FGFR1c), the endocrine hormone FGF23, and the co-receptor αKlotho. FGF23 is produced mainly by bone cells and released into the circulation, where it binds FGFRs on renal tubule cells only in the presence of membrane-bound αKlotho, which confers tissue specificity and high-affinity interaction. Binding of FGF23 to FGFR1c/αKlotho results in receptor dimerization and intracellular tyrosine kinase activation, leading to downstream signaling (mainly via ERK1/2), which suppresses renal phosphate reabsorption and 1α-hydroxylase (CYP27B1) activity, thus regulating phosphate and vitamin D metabolism. Pathological activation or inhibition of this pathway is implicated in hereditary and acquired disorders of phosphate metabolism (e.g., hypophosphatemic rickets, tumor-induced osteomalacia, CKD-mineral bone disorder), and is targeted clinically by agents such as burosumab.

Other names

FGF23–FGFR complexFGFR1c/FGF23/αKlotho complexFGF23 signaling complex

Antagonism of FGF23–FGFR binding (e.g., anti-FGF23 antibodies block ligand-receptor interaction) Downregulation of aberrant FGF23 signaling Modulation of phosphate homeostasis via inhibition of FGF23 actions