Fibroblast growth factor receptor 3c-beta-Klotho receptor complex (FGFR3c-KLB)

The Fibroblast growth factor receptor 3c-beta-Klotho receptor complex is a specialized signaling assembly required for the biological activity of the endocrine hormone Fibroblast Growth Factor 21 (FGF21). It consists of the 'c' splice variant of Fibroblast Growth Factor Receptor 3 (FGFR3c) and the obligate co-receptor beta-Klotho (KLB), which provides the necessary binding affinity for FGF21 [PMID: 17307915, 29343892]. This complex is primarily involved in the regulation of systemic metabolism, including the enhancement of insulin sensitivity, promotion of glucose uptake, and modulation of lipid metabolism in the liver and adipose tissue [UniProt Q86Z14]. Dysregulation of FGF21 signaling is associated with metabolic disorders such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatohepatitis (MASH) [PMID: 30655601]. Therapeutic strategies focus on the development of FGF21 analogs and mimetics that activate this complex to treat metabolic and fibrotic diseases [PMID: 33166244]. While FGFR1c is often considered the primary metabolic mediator, FGFR3c-KLB signaling contributes significantly to the pleiotropic effects of FGF21-based therapies.

Other names

FGFR3c-beta-Klotho complexFGFR3c-KLB complexFGF21 receptor complexFibroblast growth factor receptor 3 isoform c-beta-Klotho complex

Agonism of the FGFR3c-KLB complex to activate downstream MAPK/ERK signaling pathways, mimicking the metabolic effects of endogenous FGF21.