Fibroblast growth factor receptor 1c, 2c, or 3c:β-Klotho complex (FGFR1c/2c/3c:β-Klotho complex)

The Fibroblast growth factor receptor 1c, 2c, or 3c:β-Klotho complex is a plasma membrane receptor complex formed by heterodimerization of the β-Klotho co-receptor with one of several "IIIc" splice isoforms of FGFR (primarily FGFR1c, FGFR2c, or FGFR3c). β-Klotho acts as a high-affinity binding partner for endocrine fibroblast growth factors (notably FGF21 and FGF19), positioning them to activate FGFR kinases and initiate intracellular signaling cascades[1][3][5][6]. The specificity of ligand-receptor recognition, and by extension physiological and pharmacological effects, depends upon the pairing of particular FGFR isoforms and β-Klotho, as well as tissue expression patterns. This system is a major regulator of energy homeostasis, glucose and lipid metabolism, and is implicated in diseases such as type 2 diabetes, NAFLD/NASH, obesity, and potentially cardiovascular disease. The therapeutic targeting of this pathway is currently focused on FGF21 mimetics and β-Klotho antibodies for metabolic disorders, and novel analogs or modulators for other indications. Note: The submitted target name is non-standard: in practice, each FGFRc:β-Klotho complex is considered a separate functional target, since specificity, ligand response, and tissue distribution can differ[5][6]. If possible, specify which FGFRc isoform’s complex you are interested in for precise pharmacological annotation.

Other names

FGFR:β-Klotho complexFGFR1c:β-Klotho complexFGFR2c:β-Klotho complexFGFR3c:β-Klotho complex

Activation of FGFR signaling by ligand-induced ternary complex formation (Endocrine FGF binds β-Klotho, which scaffolds FGFR1c/2c/3c, leading to FGFR dimerization and activation) β-Klotho agonist antibodies that mimic FGF21 action by stabilizing/activating the complex Competitive antagonists (experimental) that block ligand engagement at β-Klotho or FGFR