title: Co-receptor requirements for fibroblast growth factor-19 signaling.
abstract: FGF19 is a unique member of the fibroblast growth factor (FGF) family of secreted proteins that regulates bile acid homeostasis and metabolic state in an endocrine fashion. Here we investigate the cell surface receptors required for signaling by FGF19. We show that betaKlotho, a single-pass transmembrane protein highly expressed in liver and fat, induced ERK1/2 phosphorylation in response to FGF19 treatment and significantly increased the interactions between FGF19 and FGFR4. Interestingly, our results show that alphaKlotho, another Klotho family protein related to betaKlotho, also induced ERK1/2 phosphorylation in response to FGF19 treatment and increased FGF19-FGFR4 interactions in vitro, similar to the effects of betaKlotho. In addition, heparin further enhanced the effects of both alphaKlotho and betaKlotho in FGF19 signaling and interaction experiments. These results suggest that a functional FGF19 receptor may consist of FGF receptor (FGFR) and heparan sulfate complexed with either alphaKlotho or betaKlotho.
authors: Amgen Inc., South San Francisco, California 94080, USA.
authors: Xinle
authors: X
authors: Wu
authors: Hongfei
authors: H
authors: Ge
authors: Jamila
authors: J
authors: Gupte
authors: Jennifer
authors: J
authors: Weiszmann
authors: Grant
authors: G
authors: Shimamoto
authors: Jennitte
authors: J
authors: Stevens
authors: Nessa
authors: N
authors: Hawkins
authors: Bryan
authors: B
authors: Lemon
authors: Wenyan
authors: W
authors: Shen
authors: Jing
authors: J
authors: Xu
authors: Murielle M
authors: MM
authors: Veniant
authors: Yue-Sheng
authors: YS
authors: Li
authors: Richard
authors: R
authors: Lindberg
authors: Jin-Long
authors: JL
authors: Chen
authors: Hui
authors: H
authors: Tian
authors: Yang
authors: Y
authors: Li
mesh_terms: D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004703:Endocrine System / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism* / Q000502:physiology*; D005786:Gene Expression Regulation; D005966:Glucuronidase / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D000090265:Klotho Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D014162:Transfection
chemical_list: D017077:Culture Media, Conditioned; D005346:Fibroblast Growth Factors; D005966:Glucuronidase; D006497:Heparan Sulfate; D000090265:Klotho Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C117476:FGF19 protein, human