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Regulation of Fibroblast Growth Factor-23 Signaling by Klotho*
Hiroshi Kurosu,
Yasushi Ogawa,
Masayoshi Miyoshi,
Masaya Yamamoto,
Animesh Nandi,
Kevin P. Rosenblatt,
Michel G. Baum,
Susan Schiavi¶,
Ming-Chang Hu||,
Orson W. Moe||, , and
Makoto Kuro-o1
Department of Pathology, Pediatrics, and ||Internal Medicine and ¶Applied Genomics, Genzyme Corporation, The University of Texas Southwestern Medical Center, Dallas, Texas 75390
Abstract:
The aging suppressor gene Klotho encodes a single-pass transmembraneprotein. Klotho-deficient mice exhibit a variety of aging-likephenotypes, many of which are similar to those observed in fibroblastgrowth factor-23 (FGF23)-deficient mice. To test the possibilitythat Klotho and FGF23 may function in a common signal transductionpathway(s), we investigated whether Klotho is involved in FGFsignaling. Here we show that Klotho protein directly binds tomultiple FGF receptors (FGFRs). The Klotho-FGFR complex bindsto FGF23 with higher affinity than FGFR or Klotho alone. Inaddition, Klotho significantly enhanced the ability of FGF23to induce phosphorylation of FGF receptor substrate and ERKin various types of cells. Thus, Klotho functions as a cofactoressential for activation of FGF signaling by FGF23.
Received for publication November 28, 2005.
Revision received January 18, 2006.
* This work was supported in part by grants from Endowed ScholarProgram at the University of Texas Southwestern (to M. K.),Pew Scholars Program in Biomedical Science (to M. K.), EisaiResearch Fund (to M. K.), High Impact/High Risk Research Programat The University of Texas Southwestern (to M. K.), The EllisonMedical Foundation (to M. K.), and by National Institutes ofHealth Grants R01AG19712 (to M. K.), R01AG25326 (to M. K. andK. P. R.), and R01DK065842 (to M. B.). The costs of publicationof this article were defrayed in part by the payment of pagecharges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicatethis fact.
The on-line version of this article (available at http://www.jbc.org)contains supplemental Figs. 1–4.
1 To whom correspondence should be addressed: Dept. of Pathology, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Blvd., Dallas, TX 75390-9072. Tel.: 214-648-4018; Fax: 214-648-4070; E-mail: makoto.kuroo{at}utsouthwestern.edu.
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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Endocr. Rev.
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|Abstract »|Full Text »|PDF »
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J. Clin. Endocrinol. Metab.
95, 1741-1748
|Abstract »|Full Text »|PDF »
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95, 578-585
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|Abstract »|Full Text »|PDF »
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Nephrol. Dial. Transplant.
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|Abstract »|Full Text »|PDF »
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B. S. Levine, C. R. Kleeman, and A. J. Felsenfeld (2009)
Clin. J. Am. Soc. Nephrol.
4, 1866-1877
|Abstract »|Full Text »|PDF »
Hypophosphatemia-mediated hypotension in transgenic mice overexpressing human FGF-23.
P. Liu, X. Bai, H. Wang, A. Karaplis, D. Goltzman, and D. Miao (2009)
Am J Physiol Heart Circ Physiol
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|Abstract »|Full Text »|PDF »
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S. Liu, W. Tang, J. Fang, J. Ren, H. Li, Z. Xiao, and L. D. Quarles (2009)
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|Abstract »|Full Text »|PDF »
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|Abstract »|Full Text »|PDF »
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C-terminal Tail of FGF19 Determines Its Specificity toward Klotho Co-receptors.
X. Wu, B. Lemon, X. Li, J. Gupte, J. Weiszmann, J. Stevens, N. Hawkins, W. Shen, R. Lindberg, J.-L. Chen, et al. (2008)
J. Biol. Chem.
283, 33304-33309
|Abstract »|Full Text »|PDF »
{beta}-Klotho and FGF-15/19 inhibit the apical sodium-dependent bile acid transporter in enterocytes and cholangiocytes.
J. Sinha, F. Chen, T. Miloh, R. C. Burns, Z. Yu, and B. L. Shneider (2008)
Am J Physiol Gastrointest Liver Physiol
295, G996-G1003
|Abstract »|Full Text »|PDF »
Type I Membrane Klotho Expression Is Decreased and Inversely Correlated to Serum Calcium in Primary Hyperparathyroidism.
P. Bjorklund, T. Krajisnik, G. Akerstrom, G. Westin, and T. E. Larsson (2008)
J. Clin. Endocrinol. Metab.
93, 4152-4157
|Abstract »|Full Text »|PDF »
Molecular genetic and biochemical analyses of FGF23 mutations in familial tumoral calcinosis.
H. J. Garringer, M. Malekpour, F. Esteghamat, S. M. J. Mortazavi, S. I. Davis, E. G. Farrow, X. Yu, D. E. Arking, H. C. Dietz, and K. E. White (2008)
Am J Physiol Endocrinol Metab
295, E929-E937
|Abstract »|Full Text »|PDF »
FGF-23-Klotho signaling stimulates proliferation and prevents vitamin D-induced apoptosis.
D. Medici, M. S. Razzaque, S. DeLuca, T. L. Rector, B. Hou, K. Kang, R. Goetz, M. Mohammadi, M. Kuro-o, B. R. Olsen, et al. (2008)
J. Cell Biol.
182, 459-465
|Abstract »|Full Text »|PDF »
Pathophysiology of parathyroid hyperplasia in chronic kidney disease: preclinical and clinical basis for parathyroid intervention.
S. Goto, H. Komaba, and M. Fukagawa (2008)
Clinical Kidney Journal
1, iii2-iii8
|Abstract »|Full Text »|PDF »
Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1.
S.-K. Cha, B. Ortega, H. Kurosu, K. P. Rosenblatt, M. Kuro-o, and C.-L. Huang (2008)
PNAS
105, 9805-9810
|Abstract »|Full Text »|PDF »
Cellular Signaling by Fibroblast Growth Factors (FGFs) and Their Receptors (FGFRs) in Male Reproduction.
L. M. Cotton, M. K. O'Bryan, and B. T. Hinton (2008)
Endocr. Rev.
29, 193-216
|Abstract »|Full Text »|PDF »
{beta}Klotho Is Required for Fibroblast Growth Factor (FGF) 21 Signaling through FGF Receptor (FGFR) 1c and FGFR3c.
M. Suzuki, Y. Uehara, K. Motomura-Matsuzaka, J. Oki, Y. Koyama, M. Kimura, M. Asada, A. Komi-Kuramochi, S. Oka, and T. Imamura (2008)
Mol. Endocrinol.
22, 1006-1014
|Abstract »|Full Text »|PDF »
A translocation causing increased {alpha}-Klotho level results in hypophosphatemic rickets and hyperparathyroidism.
C. A. Brownstein, F. Adler, C. Nelson-Williams, J. Iijima, P. Li, A. Imura, Y.-i. Nabeshima, M. Reyes-Mugica, T. O. Carpenter, and R. P. Lifton (2008)
PNAS
105, 3455-3460
|Abstract »|Full Text »|PDF »
Postprandial Mineral Metabolism and Secondary Hyperparathyroidism in Early CKD.
T. Isakova, O. Gutierrez, A. Shah, L. Castaldo, J. Holmes, H. Lee, and M. Wolf (2008)
J. Am. Soc. Nephrol.
19, 615-623
|Abstract »|Full Text »|PDF »
Distinct roles for intrinsic osteocyte abnormalities and systemic factors in regulation of FGF23 and bone mineralization in Hyp mice.
S. Liu, W. Tang, J. Zhou, L. Vierthaler, and L. D. Quarles (2007)
Am J Physiol Endocrinol Metab
293, E1636-E1644
|Abstract »|Full Text »|PDF »
,
Yasushi Ogawa
,
Susan Schiavi¶,
Ming-Chang Hu||,
Orson W. Moe||, , and
Makoto Kuro-o
