Human FGF-23 belongs to the FGF-19 subfamily which has three members FGF-19, 21, 23. All FGF family members are heparin binding growth factors with a core 120 amino acid (a.a.) FGF domain that allows for a common tertiary structure. They are classically considered to be paracrine factors and are known for their roles in tissue patterning and organogenesis during embryogenesis. By contrast, the FGF-19 subfamily has recently been shown to function in an endocrine manner. Members of this subfamily have poor ability of binding to heparin binding site which is a crucial factor in ligand-receptor complex formation. β-Klotho has been identified as co-factor required for FGF-19, 21, 23 signaling. It can obviously increase ligand-receptor affinity. FGF-23 is most highly expressed in bone, from which it circulates through the blood to regulate vitamin D and phosphate metabolism in kidney.
Reference:
1. Smallwood PM, Munoz-Sanjuan I, Tong P, et al. 1996. Proc Natl Acad Sci U S A. 93:9850-7.
2. Fu L, John LM, Adams SH, et al. 2004. Endocrinology. 145:2594-603.
3. Kharitonenkov A, Shiyanova TL, Koester A, et al. 2005. J Clin Invest. 115:1627-35.
4. Kurosu H, Kuro OM. 2009. Mol Cell Endocrinol. 299:72-8.
5. Lin BC, Wang M, Blackmore C, et al. 2007. J Biol Chem. 282:27277-84.
6. Kharitonenkov A, Dunbar JD, Bina HA, et al. 2008. J Cell Physiol. 215:1-7.
7. Riminucci M, Collins MT, Fedarko NS, et al. 2003. J Clin Invest. 112:683-92.
8. Shimada T, Hasegawa H, Yamazaki Y, et al. 2004. J Bone Miner Res. 19:429-35.