Endocrine FGFs and Klothos

Volume 728 of the series Advances in Experimental Medicine and Biology pp 171-182

Physiology of FGF15/19

  • Stacey A. JonesAffiliated withDrug Discovery, Research and Development, GlaxoSmithKline

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This chapter will review the various biological actions of the mouse fibroblast growth factor 15 (Fgf15) and human fibroblast growth factor 19 (FGF19). Unlike other members of the fibroblast growth factor (FGF) family, the Fgf15 and FGF19 orthologs do not share a high degree of sequence identity. Fgf15 and FGF19 are members of an atypical subfamily of FGFs that function as hormones. Due to subtle changes in tertiary structure, these FGFs have low heparin binding affinity enabling them to diffuse away from their site of secretion and signal to distant cells. FGF signaling through the FGF receptors is also different for this sub-family, requiring klotho protein cofactors rather than heparin sulfate proteoglycan. Mouse Fgf15 and human FGF19 play key roles in enterohepatic signaling, regulation of liver bile acid biosynthesis, gallbladder motility and metabolic homeostasis.