Fibroblast growth factor receptor 1–beta-Klotho complex (FGFR1–β-Klotho complex)

The **Fibroblast growth factor receptor 1–beta-Klotho complex** is a functional cell surface receptor assembly essential for mediating the action of endocrine fibroblast growth factors, notably FGF21 and FGF19[2][3][5][7]. FGFR1 (Fibroblast growth factor receptor 1) is a receptor tyrosine kinase, while β-Klotho is a single-pass transmembrane co-receptor. Endocrine FGFs do not activate FGFRs efficiently on their own; instead, β-Klotho confers ligand specificity and high-affinity binding for FGF21 and FGF19. Upon ligand binding, β-Klotho binds to FGFR1c, forming a ternary complex that triggers intracellular signaling cascades such as the RAS-MAPK-ERK, PI3K-AKT, and STAT pathways, ultimately influencing metabolism, energy homeostasis, and cellular growth[1][2][5][7]. Dysregulation or altered expression of this complex is implicated in multiple diseases, particularly metabolic and fibrotic disorders. Such complexes represent validated therapeutic targets, with several FGF21 and FGF19 analogs in clinical development for diabetes and NAFLD/NASH[2][7].

Other names

FGFR1/β-Klotho complexFGFR1c/β-Klotho complexFibroblast growth factor receptor 1 and beta-Klotho complexBeta-Klotho/FGFR1c complex

Ligand-induced activation of FGFR1 via β-Klotho-dependent binding of FGF21 or FGF19, leading to downstream signaling (RAS-MAPK, PI3K-AKT, PLCγ, STAT pathways)[2][7] Activation of the MAPK (ERK1/2) cascade and gene transcription[1][2][7] Modulation of glucose and lipid metabolism via endocrine FGF ligand action