Fibroblast growth factor receptor 1 isoform c in complex with beta-Klotho (FGFR1c/KLB)

The FGFR1c in complex with beta-Klotho (KLB) is a cell-surface signaling assembly that serves as the primary receptor for the endocrine hormone fibroblast growth factor 21 (FGF21) [1.1.1, 1.3.2]. While the fibroblast growth factor receptor 1c (FGFR1c) is a widely expressed receptor tyrosine kinase, its ability to bind and respond to FGF21 is strictly dependent on the presence of beta-Klotho, which acts as an obligatory co-receptor [1.2.1, 1.4.1]. This complex is predominantly localized in metabolic tissues, including white and brown adipose tissue, the liver, the pancreas, and the central nervous system [1.1.1, 1.4.2]. Upon activation by FGF21 or its pharmacological mimetics, the complex triggers downstream signaling pathways, most notably the MAPK/ERK pathway, which lead to increased glucose uptake, improved insulin sensitivity, and enhanced energy expenditure [1.3.2, 1.4.3]. Consequently, the FGFR1c/KLB complex is a major therapeutic target for metabolic disorders, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis (NASH) [1.2.2, 1.2.5]. Pharmacological agents targeting this complex include FGF21 analogs and bispecific antibodies designed to activate the receptor specifically in a beta-Klotho-dependent manner [1.2.2, 1.4.2].

Other names

FGFR1c-beta-Klotho complexFGF21 receptor complexKLB-FGFR1c heterocomplexFibroblast growth factor receptor 1 isoform c and beta-Klotho complex

Agonism of the FGFR1c/beta-Klotho complex to activate downstream MAPK/ERK signaling pathways, mimicking the metabolic effects of FGF21.