title: Understanding the structure-function relationship between FGF19 and its mitogenic and metabolic activities.
abstract: FGF19 differs from the classical FGFs in that it has a much-reduced heparan sulfate proteoglycan binding affinity that allows it to act as endocrine hormone. Although FGF19 regulates several different metabolic activities, it still activates downstream signaling pathways through FGF receptors, in a similar manner to that seen in classical FGFs. Aberrant FGF signaling has been implicated in tumor development, and mouse models have confirmed that FGF19 has the potential to induce hepatocellular carcinoma. Treatment with anti-FGF19 antibody suppressed tumor progression in both FGF19 transgenic mice and colon cancer cell xenograft models. FGFR4, the predominant FGF receptor expressed in the liver, may play an important role in FGF19-mediated tumorigenesis. This review reports the current advances in understanding the structure-function relationship between FGF19 and its interactions with FGFRs, its physiological activities, and its differences from FGF21. The review also discusses strategies to separate the mitogenic and metabolic activities for the development of potential therapeutic molecules based on FGF19.
authors.affiliation: Amgen Inc, South San Francisco, CA, USA.
authors.forename: Xinle
authors.initials: X
authors.lastname: Wu
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005346:Fibroblast Growth Factors / Q000737:chemistry* / Q000378:metabolism*; D006133:Growth Substances / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D006133:Growth Substances; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors