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Overview of Klotho protein. (A) Fibroblast growth factor 23 (FGF23) engages the fibroblast growth factor receptor (FGFR)-Klotho coreceptor complex that triggers cellular signaling. (B) Transmembrane Klotho with its Kl1 and Kl2 domains and the generation of soluble circulating Klotho by secretases (ADAM10 and ADAM17). (C) Structure of FGFR1c, Klotho, and FGF23 (one molecule each) as determined by Chen et al. (12). RXXR motif, proteolytic cleavage motif.
