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

The Fibroblast growth factor receptor 1–beta-Klotho (FGFR1–KLB) complex is a specialized signaling unit required for the biological activity of the endocrine hormone Fibroblast Growth Factor 21 (FGF21) (UniProt: P11362, Q86Z14). While FGFR1 is a ubiquitous receptor tyrosine kinase, its interaction with the transmembrane protein beta-Klotho provides the tissue specificity and high-affinity binding site necessary for FGF21 signaling in the liver and adipose tissue (PubMed: 29343891). Upon activation by FGF21 or its mimetics, the complex undergoes dimerization and autophosphorylation, triggering downstream pathways like MAPK/ERK that regulate glucose uptake and lipid metabolism (PubMed: 30107179). This receptor complex is a major therapeutic target for metabolic diseases, particularly metabolic dysfunction-associated steatohepatitis (MASH) and type 2 diabetes, where it helps reduce hepatic fat and improve insulin sensitivity (PubMed: 33434115). Pharmacological agents targeting this complex include FGF21 analogs such as efruxifermin and pegozafermin, as well as bispecific antibodies designed to mimic the hormone's action (PubMed: 32554450).

Other names

FGFR1c–KLB complexFGF21 receptor complexFGFR1–beta-KlothoKLB–FGFR1 complex

Agonism of the FGFR1–beta-Klotho complex to activate downstream MAPK/ERK signaling, mimicking the metabolic effects of endogenous FGF21.