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J. Biol. Chem. 281 (10): 6120-6123

© 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

Regulation of Fibroblast Growth Factor-23 Signaling by Klotho*


Hiroshi Kurosu{ddagger}, Yasushi Ogawa{ddagger}, Masayoshi Miyoshi{ddagger}, Masaya Yamamoto{ddagger}, Animesh Nandi{ddagger}, Kevin P. Rosenblatt{ddagger}, Michel G. Baum§, Susan Schiavi, Ming-Chang Hu||, Orson W. Moe||, , and Makoto Kuro-o{ddagger}1

Department of {ddagger}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 transmembrane protein. Klotho-deficient mice exhibit a variety of aging-like phenotypes, many of which are similar to those observed in fibroblast growth factor-23 (FGF23)-deficient mice. To test the possibility that Klotho and FGF23 may function in a common signal transduction pathway(s), we investigated whether Klotho is involved in FGF signaling. Here we show that Klotho protein directly binds to multiple FGF receptors (FGFRs). The Klotho-FGFR complex binds to FGF23 with higher affinity than FGFR or Klotho alone. In addition, Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. Thus, Klotho functions as a cofactor essential 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 Scholar Program at the University of Texas Southwestern (to M. K.), Pew Scholars Program in Biomedical Science (to M. K.), Eisai Research Fund (to M. K.), High Impact/High Risk Research Program at The University of Texas Southwestern (to M. K.), The Ellison Medical Foundation (to M. K.), and by National Institutes of Health Grants R01AG19712 (to M. K.), R01AG25326 (to M. K. and K. P. R.), and R01DK065842 (to M. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


The on-line version of this article (available at 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}

Dynamic regulation of FGF23 by Fam20C phosphorylation, GalNAc-T3 glycosylation, and furin proteolysis.
V. S. Tagliabracci, J. L. Engel, S. E. Wiley, J. Xiao, D. J. Gonzalez, H. Nidumanda Appaiah, A. Koller, V. Nizet, K. E. White, and J. E. Dixon (2014)
PNAS 111, 5520-5525
   Abstract »    Full Text »    PDF »
Fibroblast growth factor 23.
E. R. Smith, L. P. McMahon, and S. G. Holt (2014)
Annals of Clinical Biochemistry 51, 203-227
   Abstract »    Full Text »    PDF »
FGF23 promotes renal calcium reabsorption through the TRPV5 channel.
O. Andrukhova, A. Smorodchenko, M. Egerbacher, C. Streicher, U. Zeitz, R. Goetz, V. Shalhoub, M. Mohammadi, E. E. Pohl, B. Lanske, et al. (2014)
EMBO J. 33, 229-246
   Abstract »    Full Text »    PDF »
Regulation of renal phosphate transport by FGF23 is mediated by FGFR1 and FGFR4.
J. Gattineni, P. Alphonse, Q. Zhang, N. Mathews, C. M. Bates, and M. Baum (2014)
Am J Physiol Renal Physiol 306, F351-F358
   Abstract »    Full Text »    PDF »
Sympathetic Activation Induces Skeletal Fgf23 Expression in a Circadian Rhythm-dependent Manner.
M. Kawai, S. Kinoshita, S. Shimba, K. Ozono, and T. Michigami (2014)
J. Biol. Chem. 289, 1457-1466
   Abstract »    Full Text »    PDF »
Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia.
Y. H. Lim, D. Ovejero, J. S. Sugarman, C. M. C. DeKlotz, A. Maruri, L. F. Eichenfield, P. K. Kelley, H. Juppner, M. Gottschalk, C. J. Tifft, et al. (2014)
Hum. Mol. Genet. 23, 397-407
   Abstract »    Full Text »    PDF »
Loss of Memo, a novel FGFR regulator, results in reduced lifespan.
B. Haenzi, O. Bonny, R. Masson, S. Lienhard, J. H. Dey, M. Kuro-o, and N. E. Hynes (2014)
FASEB J 28, 327-336
   Abstract »    Full Text »    PDF »
Biochemical and Functional Characterization of the Klotho-VS Polymorphism Implicated in Aging and Disease Risk.
T. B. Tucker Zhou, G. D. King, C. Chen, and C. R. Abraham (2013)
J. Biol. Chem. 288, 36302-36311
   Abstract »    Full Text »    PDF »
Growth hormone and Klotho.
C. Schmid, M. C. Neidert, O. Tschopp, L. Sze, and R. L. Bernays (2013)
J. Endocrinol. 219, R37-R57
   Abstract »    Full Text »    PDF »
The Age-Regulating Protein Klotho Is Vital to Sustain Retinal Function.
N. J. Reish, A. Maltare, A. S. McKeown, A. M. Laszczyk, T. W. Kraft, A. K. Gross, and G. D. King (2013)
Invest. Ophthalmol. Vis. Sci. 54, 6675-6685
   Abstract »    Full Text »    PDF »
Pan-FGFR Inhibition Leads to Blockade of FGF23 Signaling, Soft Tissue Mineralization, and Cardiovascular Dysfunction.
G. M. Yanochko, A. Vitsky, J. R. Heyen, B. Hirakawa, J. L. Lam, J. May, T. Nichols, F. Sace, D. Trajkovic, and E. Blasi (2013)
Toxicol. Sci. 135, 451-464
   Abstract »    Full Text »    PDF »
Molecular Mechanisms of Fibroblast Growth Factor Signaling in Physiology and Pathology.
A. A. Belov and M. Mohammadi (2013)
Cold Spring Harb Perspect Biol 5, a015958
   Abstract »    Full Text »    PDF »
Blockade of Nonhormonal Fibroblast Growth Factors by FP-1039 Inhibits Growth of Multiple Types of Cancer.
T. C. Harding, L. Long, S. Palencia, H. Zhang, A. Sadra, K. Hestir, N. Patil, A. Levin, A. W. Hsu, D. Charych, et al. (2013)
Science Translational Medicine 5, 178ra39
   Abstract »    Full Text »    PDF »
Soluble {alpha}-Klotho: a novel serum biomarker for the activity of GH-producing pituitary adenomas.
M. C. Neidert, L. Sze, C. Zwimpfer, J. Sarnthein, B. Seifert, K. Frei, H. Leske, E. J. Rushing, C. Schmid, and R.-L. Bernays (2013)
Eur. J. Endocrinol. 168, 575-583
   Abstract »    Full Text »    PDF »
Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: a sequence suggested from a cross-sectional study.
I. Pavik, P. Jaeger, L. Ebner, C. A. Wagner, K. Petzold, D. Spichtig, D. Poster, R. P. Wuthrich, S. Russmann, and A. L. Serra (2013)
Nephrol. Dial. Transplant. 28, 352-359
   Abstract »    Full Text »    PDF »
Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo.
S. J. Quinn, A. R. B. Thomsen, J. L. Pang, L. Kantham, H. Brauner-Osborne, M. Pollak, D. Goltzman, and E. M. Brown (2013)
Am J Physiol Endocrinol Metab 304, E310-E320
   Abstract »    Full Text »    PDF »
The Antiaging Protein Klotho Enhances Oligodendrocyte Maturation and Myelination of the CNS.
C.-D. Chen, J. A. Sloane, H. Li, N. Aytan, E. L. Giannaris, E. Zeldich, J. D. Hinman, A. Dedeoglu, D. L. Rosene, R. Bansal, et al. (2013)
J. Neurosci. 33, 1927-1939
   Abstract »    Full Text »    PDF »
FGF23 Suppresses Chondrocyte Proliferation in the Presence of Soluble {alpha}-Klotho both in Vitro and in Vivo.
M. Kawai, S. Kinoshita, A. Kimoto, Y. Hasegawa, K. Miyagawa, M. Yamazaki, Y. Ohata, K. Ozono, and T. Michigami (2013)
J. Biol. Chem. 288, 2414-2427
   Abstract »    Full Text »    PDF »
Satellite Cells and the Muscle Stem Cell Niche.
H. Yin, F. Price, and M. A. Rudnicki (2013)
Physiol Rev 93, 23-67
   Abstract »    Full Text »    PDF »
Fibroblast growth factor 23 and soluble klotho in children with chronic kidney disease.
M. Wan, C. Smith, V. Shah, A. Gullet, D. Wells, L. Rees, and R. Shroff (2013)
Nephrol. Dial. Transplant. 28, 153-161
   Abstract »    Full Text »    PDF »
Expression of fgf23 and {alpha}klotho in developing embryonic tissues and adult kidney of the zebrafish, Danio rerio.
S. Mangos, A. P. Amaral, C. Faul, H. Juppner, J. Reiser, and M. Wolf (2012)
Nephrol. Dial. Transplant. 27, 4314-4322
   Abstract »    Full Text »    PDF »
Serum level of fibroblast growth factor 23 in maintenance renal transplant patients.
A. I. Sanchez Fructuoso, M. L. Maestro, I. Perez-Flores, R. Valero, S. Rafael, S. Veganzones, N. Calvo, V. De la Orden, J. C. De la Flor, F. Valga, et al. (2012)
Nephrol. Dial. Transplant. 27, 4227-4235
   Abstract »    Full Text »    PDF »
Promoter methylation confers kidney-specific expression of the Klotho gene.
M. Azuma, D. Koyama, J. Kikuchi, H. Yoshizawa, D. Thasinas, K. Shiizaki, M. Kuro-o, Y. Furukawa, and E. Kusano (2012)
FASEB J 26, 4264-4274
   Abstract »    Full Text »    PDF »
Conversion of a Paracrine Fibroblast Growth Factor into an Endocrine Fibroblast Growth Factor.
R. Goetz, M. Ohnishi, S. Kir, H. Kurosu, L. Wang, J. Pastor, J. Ma, W. Gai, M. Kuro-o, M. S. Razzaque, et al. (2012)
J. Biol. Chem. 287, 29134-29146
   Abstract »    Full Text »    PDF »
The emerging role of Klotho in clinical nephrology.
M. C. Hu, M. Kuro-o, and O. W. Moe (2012)
Nephrol. Dial. Transplant. 27, 2650-2657
   Abstract »    Full Text »    PDF »
Fibroblast growth factor receptors in breast cancer: expression, downstream effects, and possible drug targets.
M. Tenhagen, P. J. van Diest, I. A. Ivanova, E. van der Wall, and P. van der Groep (2012)
Endocr. Relat. Cancer 19, R115-R129
   Abstract »    Full Text »    PDF »
Dynamics and Distribution of Klotho{beta} (KLB) and Fibroblast Growth Factor Receptor-1 (FGFR1) in Living Cells Reveal the Fibroblast Growth Factor-21 (FGF21)-induced Receptor Complex.
A. Y. K. Ming, E. Yoo, E. N. Vorontsov, S. M. Altamentova, D. M. Kilkenny, and J. V. Rocheleau (2012)
J. Biol. Chem. 287, 19997-20006
   Abstract »    Full Text »    PDF »
Changes in fibroblast growth factor 23 during treatment of secondary hyperparathyroidism with alfacalcidol or paricalcitol.
D. Hansen, K. Rasmussen, S. M. Pedersen, L. M. Rasmussen, and L. Brandi (2012)
Nephrol. Dial. Transplant. 27, 2263-2269
   Abstract »    Full Text »    PDF »
Signaling in Cell Differentiation and Morphogenesis.
M. A. Basson (2012)
Cold Spring Harb Perspect Biol 4, a008151
   Abstract »    Full Text »    PDF »
Klotho Coreceptors Inhibit Signaling by Paracrine Fibroblast Growth Factor 8 Subfamily Ligands.
R. Goetz, M. Ohnishi, X. Ding, H. Kurosu, L. Wang, J. Akiyoshi, J. Ma, W. Gai, Y. Sidis, N. Pitteloud, et al. (2012)
Mol. Cell. Biol. 32, 1944-1954
   Abstract »    Full Text »    PDF »
Vascular Klotho Deficiency Potentiates the Development of Human Artery Calcification and Mediates Resistance to Fibroblast Growth Factor 23.
K. Lim, T.-S. Lu, G. Molostvov, C. Lee, F. T. Lam, D. Zehnder, and L.-L. Hsiao (2012)
Circulation 125, 2243-2255
   Abstract »    Full Text »    PDF »
Effects of cinacalcet treatment on serum soluble Klotho levels in haemodialysis patients with secondary hyperparathyroidism.
H. Komaba, M. Koizumi, H. Tanaka, H. Takahashi, K. Sawada, T. Kakuta, and M. Fukagawa (2012)
Nephrol. Dial. Transplant. 27, 1967-1969
   Abstract »    Full Text »    PDF »
Measurement of serum soluble Klotho levels in CKD 5D patients: useful tool or dispensable biomarker?.
D. Fliser, S. Seiler, G. H. Heine, and M. Ketteler (2012)
Nephrol. Dial. Transplant. 27, 1702-1703
   Full Text »    PDF »
Fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin D3-enhanced duodenal calcium transport in male mice.
P. Khuituan, J. Teerapornpuntakit, K. Wongdee, P. Suntornsaratoon, N. Konthapakdee, J. Sangsaksri, C. Sripong, N. Krishnamra, and N. Charoenphandhu (2012)
Am J Physiol Endocrinol Metab 302, E903-E913
   Abstract »    Full Text »    PDF »
Molecular Pathways: Fibroblast Growth Factor Signaling: A New Therapeutic Opportunity in Cancer.
A. N. Brooks, E. Kilgour, and P. D. Smith (2012)
Clin. Cancer Res. 18, 1855-1862
   Abstract »    Full Text »    PDF »
Endocrine fibroblast growth factors 15/19 and 21: from feast to famine.
M. J. Potthoff, S. A. Kliewer, and D. J. Mangelsdorf (2012)
Genes & Dev. 26, 312-324
   Abstract »    Full Text »    PDF »
Plasticity in Interactions of Fibroblast Growth Factor 1 (FGF1) N Terminus with FGF Receptors Underlies Promiscuity of FGF1.
A. Beenken, A. V. Eliseenkova, O. A. Ibrahimi, S. K. Olsen, and M. Mohammadi (2012)
J. Biol. Chem. 287, 3067-3078
   Abstract »    Full Text »    PDF »
Regulation and Function of the FGF23/Klotho Endocrine Pathways.
A. Martin, V. David, and L. D. Quarles (2012)
Physiol Rev 92, 131-155
   Abstract »    Full Text »    PDF »
Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice.
E. G. Farrow, X. Yu, L. J. Summers, S. I. Davis, J. C. Fleet, M. R. Allen, A. G. Robling, K. R. Stayrook, V. Jideonwo, M. J. Magers, et al. (2011)
PNAS 108, E1146-E1155
   Abstract »    Full Text »    PDF »
Cross Talk Between the Renin-Angiotensin-Aldosterone System and Vitamin D-FGF-23-klotho in Chronic Kidney Disease.
M. H. de Borst, M. G. Vervloet, P. M. ter Wee, and G. Navis (2011)
J. Am. Soc. Nephrol. 22, 1603-1609
   Abstract »    Full Text »    PDF »
Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf23 expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling.
A. Martin, S. Liu, V. David, H. Li, A. Karydis, J. Q. Feng, and L. D. Quarles (2011)
FASEB J 25, 2551-2562
   Abstract »    Full Text »    PDF »
Regulation of serum 1,25(OH)2Vitamin D3 levels by fibroblast growth factor 23 is mediated by FGF receptors 3 and 4.
J. Gattineni, K. Twombley, R. Goetz, M. Mohammadi, and M. Baum (2011)
Am J Physiol Renal Physiol 301, F371-F377
   Abstract »    Full Text »    PDF »
KL1 Internal Repeat Mediates Klotho Tumor Suppressor Activities and Inhibits bFGF and IGF-I Signaling in Pancreatic Cancer.
L. Abramovitz, T. Rubinek, H. Ligumsky, S. Bose, I. Barshack, C. Avivi, B. Kaufman, and I. Wolf (2011)
Clin. Cancer Res. 17, 4254-4266
   Abstract »    Full Text »    PDF »
Tumor-induced osteomalacia.
W. H. Chong, A. A. Molinolo, C. C. Chen, and M. T. Collins (2011)
Endocr. Relat. Cancer 18, R53-R77
   Abstract »    Full Text »    PDF »
Klotho Inhibits Transforming Growth Factor-{beta}1 (TGF-{beta}1) Signaling and Suppresses Renal Fibrosis and Cancer Metastasis in Mice.
S. Doi, Y. Zou, O. Togao, J. V. Pastor, G. B. John, L. Wang, K. Shiizaki, R. Gotschall, S. Schiavi, N. Yorioka, et al. (2011)
J. Biol. Chem. 286, 8655-8665
   Abstract »    Full Text »    PDF »
Compound deletion of Fgfr3 and Fgfr4 partially rescues the Hyp mouse phenotype.
H. Li, A. Martin, V. David, and L. D. Quarles (2011)
Am J Physiol Endocrinol Metab 300, E508-E517
   Abstract »    Full Text »    PDF »
The Cooperation of FGF Receptor and Klotho Is Involved in Excretory Canal Development and Regulation of Metabolic Homeostasis in Caenorhabditis elegans.
U. M. Polanska, E. Edwards, D. G. Fernig, and T. K. Kinnunen (2011)
J. Biol. Chem. 286, 5657-5666
   Abstract »    Full Text »    PDF »
Cellular ATP Synthesis Mediated by Type III Sodium-dependent Phosphate Transporter Pit-1 Is Critical to Chondrogenesis.
A. Sugita, S. Kawai, T. Hayashibara, A. Amano, T. Ooshima, T. Michigami, H. Yoshikawa, and T. Yoneda (2011)
J. Biol. Chem. 286, 3094-3103
   Abstract »    Full Text »    PDF »
Klotho: An Elixir of Youth for the Vasculature?.
R. Shroff and C. M. Shanahan (2011)
J. Am. Soc. Nephrol. 22, 5-7
   Full Text »    PDF »
Circulating Fibroblast Growth Factor-23 Is Associated With Fat Mass and Dyslipidemia in Two Independent Cohorts of Elderly Individuals.
M. A. I. Mirza, J. Alsio, A. Hammarstedt, R. G. Erben, K. Michaelsson, A. Tivesten, R. Marsell, E. Orwoll, M. K. Karlsson, O. Ljunggren, et al. (2011)
Arterioscler Thromb Vasc Biol 31, 219-227
   Abstract »    Full Text »    PDF »
Klotho Deficiency Causes Vascular Calcification in Chronic Kidney Disease.
M. C. Hu, M. Shi, J. Zhang, H. Quinones, C. Griffith, M. Kuro-o, and O. W. Moe (2011)
J. Am. Soc. Nephrol. 22, 124-136
   Abstract »    Full Text »    PDF »
PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop.
V. Lavi-Moshayoff, G. Wasserman, T. Meir, J. Silver, and T. Naveh-Many (2010)
Am J Physiol Renal Physiol 299, F882-F889
   Abstract »    Full Text »    PDF »
Metabolic Regulator {beta}Klotho Interacts with Fibroblast Growth Factor Receptor 4 (FGFR4) to Induce Apoptosis and Inhibit Tumor Cell Proliferation.
Y. Luo, C. Yang, W. Lu, R. Xie, C. Jin, P. Huang, F. Wang, and W. L. McKeehan (2010)
J. Biol. Chem. 285, 30069-30078
   Abstract »    Full Text »    PDF »
Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule.
M. C. Hu, M. Shi, J. Zhang, J. Pastor, T. Nakatani, B. Lanske, M. S. Razzaque, K. P. Rosenblatt, M. G. Baum, M. Kuro-o, et al. (2010)
FASEB J 24, 3438-3450
   Abstract »    Full Text »    PDF »
Reciprocal Control of 1,25-Dihydroxyvitamin D and FGF23 Formation Involving the FGF23/Klotho System.
D. Prie and G. Friedlander (2010)
Clin. J. Am. Soc. Nephrol. 5, 1717-1722
   Abstract »    Full Text »    PDF »
Forging Forward with 10 Burning Questions on FGF23 in Kidney Disease.
M. Wolf (2010)
J. Am. Soc. Nephrol. 21, 1427-1435
   Abstract »    Full Text »    PDF »
Separating mitogenic and metabolic activities of fibroblast growth factor 19 (FGF19).
X. Wu, H. Ge, B. Lemon, S. Vonderfecht, H. Baribault, J. Weiszmann, J. Gupte, J. Gardner, R. Lindberg, Z. Wang, et al. (2010)
PNAS 107, 14158-14163
   Abstract »    Full Text »    PDF »
Phosphate homeostasis and the renal-gastrointestinal axis.
J. Marks, E. S. Debnam, and R. J. Unwin (2010)
Am J Physiol Renal Physiol 299, F285-F296
   Abstract »    Full Text »    PDF »
Mammary Gland Growth Factors: Roles in Normal Development and in Cancer.
N. E. Hynes and C. J. Watson (2010)
Cold Spring Harb Perspect Biol 2, a003186
   Abstract »    Full Text »    PDF »
FGF23 Fails to Inhibit Uremic Parathyroid Glands.
R. Canalejo, A. Canalejo, J. M. Martinez-Moreno, M. E. Rodriguez-Ortiz, J. C. Estepa, F. J. Mendoza, J. R. Munoz-Castaneda, V. Shalhoub, Y. Almaden, and M. Rodriguez (2010)
J. Am. Soc. Nephrol. 21, 1125-1135
   Abstract »    Full Text »    PDF »
Phosphaturic action of fibroblast growth factor 23 in Npt2 null mice.
Y. Tomoe, H. Segawa, K. Shiozawa, I. Kaneko, R. Tominaga, E. Hanabusa, F. Aranami, J. Furutani, S. Kuwahara, S. Tatsumi, et al. (2010)
Am J Physiol Renal Physiol 298, F1341-F1350
   Abstract »    Full Text »    PDF »
Relevant use of Klotho in FGF19 subfamily signaling system in vivo.
K.-i. Tomiyama, R. Maeda, I. Urakawa, Y. Yamazaki, T. Tanaka, S. Ito, Y. Nabeshima, T. Tomita, S. Odori, K. Hosoda, et al. (2010)
PNAS 107, 1666-1671
   Abstract »    Full Text »    PDF »
Nuclear Isoforms of Fibroblast Growth Factor 2 Are Novel Inducers of Hypophosphatemia via Modulation of FGF23 and KLOTHO.
L. Xiao, T. Naganawa, J. Lorenzo, T. O. Carpenter, J. D. Coffin, and M. M. Hurley (2010)
J. Biol. Chem. 285, 2834-2846
   Abstract »    Full Text »    PDF »
Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation.
R. Goetz, Y. Nakada, M. C. Hu, H. Kurosu, L. Wang, T. Nakatani, M. Shi, A. V. Eliseenkova, M. S. Razzaque, O. W. Moe, et al. (2010)
PNAS 107, 407-412
   Abstract »    Full Text »    PDF »
Fibroblast growth factor 23 and its role in phosphate homeostasis.
I. Ramon, P. Kleynen, J.-J. Body, and R. Karmali (2010)
Eur. J. Endocrinol. 162, 1-10
   Abstract »    Full Text »    PDF »
Klotho reduces apoptosis in experimental ischaemic acute kidney injury via HSP-70.
H. Sugiura, T. Yoshida, M. Mitobe, S. Yoshida, S. Shiohira, K. Nitta, and K. Tsuchiya (2010)
Nephrol. Dial. Transplant. 25, 60-68
   Abstract »    Full Text »    PDF »
A novel regulatory mechanism for Fgf18 signaling involving cysteine-rich FGF receptor (Cfr) and delta-like protein (Dlk).
Y. Miyaoka, M. Tanaka, T. Imamura, S. Takada, and A. Miyajima (2010)
Development 137, 159-167
   Abstract »    Full Text »    PDF »
New Approaches to Pathogenesis and Management of Hypertension.
E. Ritz, H Krum, M Schlaich, R Whitbourn, P. Sobotka, J Sadowski, K Bartus, B Kapelak, A Walton, H Sievert, et al. (2009)
Clin. J. Am. Soc. Nephrol. 4, 1886-1891
   Full Text »    PDF »
Inactivation of klotho function induces hyperphosphatemia even in presence of high serum fibroblast growth factor 23 levels in a genetically engineered hypophosphatemic (Hyp) mouse model.
T. Nakatani, M. Ohnishi, and M. S. Razzaque (2009)
FASEB J 23, 3702-3711
   Abstract »    Full Text »    PDF »
The Journey From Vitamin D-Resistant Rickets to the Regulation of Renal Phosphate Transport.
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 297, H1514-H1520
   Abstract »    Full Text »    PDF »
FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1.
J. Gattineni, C. Bates, K. Twombley, V. Dwarakanath, M. L. Robinson, R. Goetz, M. Mohammadi, and M. Baum (2009)
Am J Physiol Renal Physiol 297, F282-F291
   Abstract »    Full Text »    PDF »
Regulation of Renal Outer Medullary Potassium Channel and Renal K+ Excretion by Klotho.
S.-K. Cha, M.-C. Hu, H. Kurosu, M. Kuro-o, O. Moe, and C.-L. Huang (2009)
Mol. Pharmacol. 76, 38-46
   Abstract »    Full Text »    PDF »
Klotho in chronic kidney disease--What's new?.
M. Kuro-o (2009)
Nephrol. Dial. Transplant. 24, 1705-1708
   Full Text »    PDF »
FGF15/FGFR4 Integrates Growth Factor Signaling with Hepatic Bile Acid Metabolism and Insulin Action.
D.-J. Shin and T. F. Osborne (2009)
J. Biol. Chem. 284, 11110-11120
   Abstract »    Full Text »    PDF »
FGF23-mediated regulation of systemic phosphate homeostasis: is Klotho an essential player?.
M. S. Razzaque (2009)
Am J Physiol Renal Physiol 296, F470-F476
   Abstract »    Full Text »    PDF »
Novel Mechanisms in the Regulation of Phosphorus Homeostasis.
T. Berndt and R. Kumar (2009)
Physiology 24, 17-25
   Abstract »    Full Text »    PDF »
In vivo genetic evidence for klotho-dependent, fibroblast growth factor 23 (Fgf23) -mediated regulation of systemic phosphate homeostasis.
T. Nakatani, B. Sarraj, M. Ohnishi, M. J. Densmore, T. Taguchi, R. Goetz, M. Mohammadi, B. Lanske, and M. S. Razzaque (2009)
FASEB J 23, 433-441
   Abstract »    Full Text »    PDF »
FGFR3 and FGFR4 Do not Mediate Renal Effects of FGF23.
S. Liu, L. Vierthaler, W. Tang, J. Zhou, and L. D. Quarles (2008)
J. Am. Soc. Nephrol. 19, 2342-2350
   Abstract »    Full Text »    PDF »
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 »
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 »
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 »

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