Tags

Type your tag names separated by a space and hit enter

Klotho converts canonical FGF receptor into a specific receptor for FGF23.
Nature. 2006 Dec 07; 444(7120):770-4.Nat

Abstract

FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions, whereas most other family members are thought to regulate various cell functions at a local level. The renotropic activity of circulating FGF23 indicates the possible presence of an FGF23-specific receptor in the kidney. Here we show that a previously undescribed receptor conversion by Klotho, a senescence-related molecule, generates the FGF23 receptor. Using a renal homogenate, we found that Klotho binds to FGF23. Forced expression of Klotho enabled the high-affinity binding of FGF23 to the cell surface and restored the ability of a renal cell line to respond to FGF23 treatment. Moreover, FGF23 incompetence was induced by injecting wild-type mice with an anti-Klotho monoclonal antibody. Thus, Klotho is essential for endogenous FGF23 function. Because Klotho alone seemed to be incapable of intracellular signalling, we searched for other components of the FGF23 receptor and found FGFR1(IIIc), which was directly converted by Klotho into the FGF23 receptor. Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. These findings provide insights into the diversity and specificity of interactions between FGF and FGF receptors.

Authors+Show Affiliations

Pharmaceutical Research Laboratories, Kirin Brewery Co., Ltd, 3 Miyahara, Takasaki, Gunma 370-1295, Japan. iurakawa@kirin.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17086194

Citation

Urakawa, Itaru, et al. "Klotho Converts Canonical FGF Receptor Into a Specific Receptor for FGF23." Nature, vol. 444, no. 7120, 2006, pp. 770-4.
Urakawa I, Yamazaki Y, Shimada T, et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. 2006;444(7120):770-4.
Urakawa, I., Yamazaki, Y., Shimada, T., Iijima, K., Hasegawa, H., Okawa, K., Fujita, T., Fukumoto, S., & Yamashita, T. (2006). Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature, 444(7120), 770-4.
Urakawa I, et al. Klotho Converts Canonical FGF Receptor Into a Specific Receptor for FGF23. Nature. 2006 Dec 7;444(7120):770-4. PubMed PMID: 17086194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Klotho converts canonical FGF receptor into a specific receptor for FGF23. AU - Urakawa,Itaru, AU - Yamazaki,Yuji, AU - Shimada,Takashi, AU - Iijima,Kousuke, AU - Hasegawa,Hisashi, AU - Okawa,Katsuya, AU - Fujita,Toshiro, AU - Fukumoto,Seiji, AU - Yamashita,Takeyoshi, Y1 - 2006/10/29/ PY - 2006/04/12/received PY - 2006/10/09/accepted PY - 2006/11/7/pubmed PY - 2007/1/5/medline PY - 2006/11/7/entrez SP - 770 EP - 4 JF - Nature JO - Nature VL - 444 IS - 7120 N2 - FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions, whereas most other family members are thought to regulate various cell functions at a local level. The renotropic activity of circulating FGF23 indicates the possible presence of an FGF23-specific receptor in the kidney. Here we show that a previously undescribed receptor conversion by Klotho, a senescence-related molecule, generates the FGF23 receptor. Using a renal homogenate, we found that Klotho binds to FGF23. Forced expression of Klotho enabled the high-affinity binding of FGF23 to the cell surface and restored the ability of a renal cell line to respond to FGF23 treatment. Moreover, FGF23 incompetence was induced by injecting wild-type mice with an anti-Klotho monoclonal antibody. Thus, Klotho is essential for endogenous FGF23 function. Because Klotho alone seemed to be incapable of intracellular signalling, we searched for other components of the FGF23 receptor and found FGFR1(IIIc), which was directly converted by Klotho into the FGF23 receptor. Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. These findings provide insights into the diversity and specificity of interactions between FGF and FGF receptors. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/17086194/Klotho_converts_canonical_FGF_receptor_into_a_specific_receptor_for_FGF23_ L2 - https://doi.org/10.1038/nature05315 DB - PRIME DP - Unbound Medicine ER -