Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 14 March 2006
Vol. 2006, Issue 326, p. tw92
[DOI: 10.1126/stke.3262006tw92]

EDITORS' CHOICE

GROWTH FACTORS Fated to Promote FGF23 Signaling

Klotho, a single-pass transmembrane protein expressed predominantly in kidney that is named for the Fate that spins the thread of life, appears to suppress aging: Klotho overexpression extends the life span in mice, whereas Klotho loss-of-function mutations lead to aging-like phenotypes. Although the Klotho extracellular domain may be shed to act as a humoral factor, the role of the full transmembrane form is unknown. Noting that the phenotypes of mice lacking Klotho resemble those of mice lacking fibroblast growth factor-23 (FGF23), Kurosu et al. investigated possible interactions between Klotho and FGF signaling. Immunoprecipitation analysis revealed that Klotho associated with various FGF receptors (FGFRs) coexpressed in 293 cells stably transfected with Klotho. Although the Klotho extracellular domain did not bind FGF23 directly, Klotho enhanced FGF23 binding. Moreover, Klotho expression increased phosphorylation of FGF receptor substrate-2α and p44/42 mitogen-activated protein kinase (MAPK) in response to treatment with FGF23. Thus, the authors conclude that Klotho acts as a cofactor to promote FGF23 signaling.

H. Kurosu, Y. Ogawa, M. Miyoshi, M. Yamamoto, A. Nandi, K. P. Rosenblatt, M. G. Baum, S. Schiavi, M.-C. Hu, O. W. Moe, M. Kuro-o, Regulation of fibroblast growth factor-23 signaling by Klotho. J. Biol. Chem. 281, 6120-6123 (2006). [Abstract] [Full Text]

Citation: Fated to Promote FGF23 Signaling. Sci. STKE 2006, tw92 (2006).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882