| Structural highlights
5w21 is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Gene: | KL (HUMAN), FGF23, HYPF, UNQ3027/PRO9828 (HUMAN), FGFR1, BFGFR, CEK, FGFBR, FLG, FLT2, HBGFR (HUMAN) |
| Activity: | Beta-glucuronidase, with EC number 3.2.1.31 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[KLOT_HUMAN] Familial tumoral calcinosis. The disease is caused by mutations affecting the gene represented in this entry. [FGFR1_HUMAN] Defects in FGFR1 are a cause of Pfeiffer syndrome (PS) [MIM:101600]; also known as acrocephalosyndactyly type V (ACS5). PS is characterized by craniosynostosis (premature fusion of the skull sutures) with deviation and enlargement of the thumbs and great toes, brachymesophalangy, with phalangeal ankylosis and a varying degree of soft tissue syndactyly.[1] [2] Defects in FGFR1 are the cause of hypogonadotropic hypogonadism 2 with or without anosmia (HH2) [MIM:147950]. A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).[3] [4] [5] [6] [7] [8] [9] [10] [11] [12] Defects in FGFR1 are the cause of osteoglophonic dysplasia (OGD) [MIM:166250]; also known as osteoglophonic dwarfism. OGD is characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant.[13] [14] [15] Defects in FGFR1 are the cause of trigonocephaly type 1 (TRIGNO1) [MIM:190440]. A keel-shaped deformation of the forehead resulting from premature fusion of the frontal suture. Trigonocephaly may occur also as a part of a syndrome.[16] [17] Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Translocation t(8;13)(p11;q12) with ZMYM2. SCLL usually presents as lymphoblastic lymphoma in association with a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow.[18] Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1OP. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP2-FGFR1, FGFR1OP-FGFR1 or FGFR1-FGFR1OP may exhibit constitutive kinase activity and be responsible for the transforming activity. Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(8;9)(p12;q33) with CEP110. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion protein CEP110-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity. [FGF23_HUMAN] Defects in FGF23 are the cause of autosomal dominant hypophosphataemic rickets (ADHR) [MIM:193100]. ADHR is characterized by low serum phosphorus concentrations, rickets, osteomalacia, leg deformities, short stature, bone pain and dental abscesses.[19] [20] [21] Defects in FGF23 are a cause of hyperphosphatemic familial tumoral calcinosis (HFTC) [MIM:211900]. HFTC is a severe autosomal recessive metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues.[22]
Function
[KLOT_HUMAN] May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity). The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling. [FGFR1_HUMAN] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation.[23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [FGF23_HUMAN] Regulator of phosphate homeostasis. Inhibits renal tubular phosphate transport by reducing SLC34A1 levels. Upregulates EGR1 expression in the presence of KL (By similarity). Acts directly on the parathyroid to decrease PTH secretion (By similarity). Regulator of vitamin-D metabolism. Negatively regulates osteoblast differentiation and matrix mineralization.[41] [42] [43] [44] [45]
Publication Abstract from PubMed
The ageing suppressor alpha-klotho binds to the fibroblast growth factor receptor (FGFR). This commits FGFR to respond to FGF23, a key hormone in the regulation of mineral ion and vitamin D homeostasis. The role and mechanism of this co-receptor are unknown. Here we present the atomic structure of a 1:1:1 ternary complex that consists of the shed extracellular domain of alpha-klotho, the FGFR1c ligand-binding domain, and FGF23. In this complex, alpha-klotho simultaneously tethers FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23-FGFR1c proximity and conferring stability. Dimerization of the stabilized ternary complexes and receptor activation remain dependent on the binding of heparan sulfate, a mandatory cofactor of paracrine FGF signalling. The structure of alpha-klotho is incompatible with its purported glycosidase activity. Thus, shed alpha-klotho functions as an on-demand non-enzymatic scaffold protein that promotes FGF23 signalling.
alpha-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling.,Chen G, Liu Y, Goetz R, Fu L, Jayaraman S, Hu MC, Moe OW, Liang G, Li X, Mohammadi M Nature. 2018 Jan 25;553(7689):461-466. doi: 10.1038/nature25451. Epub 2018 Jan, 17. PMID:29342138[46]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Miura K, Miura S, Yoshiura K, Seminara S, Hamaguchi D, Niikawa N, Masuzaki H. A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1. Hum Reprod. 2010 Apr;25(4):1076-80. doi: 10.1093/humrep/deq006. Epub 2010 Feb 6. PMID:20139426 doi:10.1093/humrep/deq006
- ↑ Muenke M, Schell U, Hehr A, Robin NH, Losken HW, Schinzel A, Pulleyn LJ, Rutland P, Reardon W, Malcolm S, et al.. A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome. Nat Genet. 1994 Nov;8(3):269-74. PMID:7874169 doi:http://dx.doi.org/10.1038/ng1194-269
- ↑ Miura K, Miura S, Yoshiura K, Seminara S, Hamaguchi D, Niikawa N, Masuzaki H. A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1. Hum Reprod. 2010 Apr;25(4):1076-80. doi: 10.1093/humrep/deq006. Epub 2010 Feb 6. PMID:20139426 doi:10.1093/humrep/deq006
- ↑ Dode C, Levilliers J, Dupont JM, De Paepe A, Le Du N, Soussi-Yanicostas N, Coimbra RS, Delmaghani S, Compain-Nouaille S, Baverel F, Pecheux C, Le Tessier D, Cruaud C, Delpech M, Speleman F, Vermeulen S, Amalfitano A, Bachelot Y, Bouchard P, Cabrol S, Carel JC, Delemarre-van de Waal H, Goulet-Salmon B, Kottler ML, Richard O, Sanchez-Franco F, Saura R, Young J, Petit C, Hardelin JP. Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nat Genet. 2003 Apr;33(4):463-5. Epub 2003 Mar 10. PMID:12627230 doi:10.1038/ng1122
- ↑ Sato N, Katsumata N, Kagami M, Hasegawa T, Hori N, Kawakita S, Minowada S, Shimotsuka A, Shishiba Y, Yokozawa M, Yasuda T, Nagasaki K, Hasegawa D, Hasegawa Y, Tachibana K, Naiki Y, Horikawa R, Tanaka T, Ogata T. Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients. J Clin Endocrinol Metab. 2004 Mar;89(3):1079-88. PMID:15001591
- ↑ Albuisson J, Pecheux C, Carel JC, Lacombe D, Leheup B, Lapuzina P, Bouchard P, Legius E, Matthijs G, Wasniewska M, Delpech M, Young J, Hardelin JP, Dode C. Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2). Hum Mutat. 2005 Jan;25(1):98-9. PMID:15605412 doi:10.1002/humu.9298
- ↑ Sato N, Hasegawa T, Hori N, Fukami M, Yoshimura Y, Ogata T. Gonadotrophin therapy in Kallmann syndrome caused by heterozygous mutations of the gene for fibroblast growth factor receptor 1: report of three families: case report. Hum Reprod. 2005 Aug;20(8):2173-8. Epub 2005 Apr 21. PMID:15845591 doi:dei052
- ↑ Trarbach EB, Costa EM, Versiani B, de Castro M, Baptista MT, Garmes HM, de Mendonca BB, Latronico AC. Novel fibroblast growth factor receptor 1 mutations in patients with congenital hypogonadotropic hypogonadism with and without anosmia. J Clin Endocrinol Metab. 2006 Oct;91(10):4006-12. Epub 2006 Aug 1. PMID:16882753 doi:10.1210/jc.2005-2793
- ↑ Pitteloud N, Meysing A, Quinton R, Acierno JS Jr, Dwyer AA, Plummer L, Fliers E, Boepple P, Hayes F, Seminara S, Hughes VA, Ma J, Bouloux P, Mohammadi M, Crowley WF Jr. Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes. Mol Cell Endocrinol. 2006 Jul 25;254-255:60-9. Epub 2006 Jun 9. PMID:16764984 doi:S0303-7207(06)00223-1
- ↑ Zenaty D, Bretones P, Lambe C, Guemas I, David M, Leger J, de Roux N. Paediatric phenotype of Kallmann syndrome due to mutations of fibroblast growth factor receptor 1 (FGFR1). Mol Cell Endocrinol. 2006 Jul 25;254-255:78-83. Epub 2006 Jun 6. PMID:16757108 doi:10.1016/j.mce.2006.04.006
- ↑ Pitteloud N, Acierno JS Jr, Meysing A, Eliseenkova AV, Ma J, Ibrahimi OA, Metzger DL, Hayes FJ, Dwyer AA, Hughes VA, Yialamas M, Hall JE, Grant E, Mohammadi M, Crowley WF Jr. Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6281-6. Epub 2006 Apr 10. PMID:16606836 doi:0600962103
- ↑ Dode C, Fouveaut C, Mortier G, Janssens S, Bertherat J, Mahoudeau J, Kottler ML, Chabrolle C, Gancel A, Francois I, Devriendt K, Wolczynski S, Pugeat M, Pineiro-Garcia A, Murat A, Bouchard P, Young J, Delpech M, Hardelin JP. Novel FGFR1 sequence variants in Kallmann syndrome, and genetic evidence that the FGFR1c isoform is required in olfactory bulb and palate morphogenesis. Hum Mutat. 2007 Jan;28(1):97-8. PMID:17154279 doi:10.1002/humu.9470
- ↑ Miura K, Miura S, Yoshiura K, Seminara S, Hamaguchi D, Niikawa N, Masuzaki H. A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1. Hum Reprod. 2010 Apr;25(4):1076-80. doi: 10.1093/humrep/deq006. Epub 2010 Feb 6. PMID:20139426 doi:10.1093/humrep/deq006
- ↑ White KE, Cabral JM, Davis SI, Fishburn T, Evans WE, Ichikawa S, Fields J, Yu X, Shaw NJ, McLellan NJ, McKeown C, Fitzpatrick D, Yu K, Ornitz DM, Econs MJ. Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation. Am J Hum Genet. 2005 Feb;76(2):361-7. Epub 2004 Dec 28. PMID:15625620 doi:S0002-9297(07)62588-9
- ↑ Farrow EG, Davis SI, Mooney SD, Beighton P, Mascarenhas L, Gutierrez YR, Pitukcheewanont P, White KE. Extended mutational analyses of FGFR1 in osteoglophonic dysplasia. Am J Med Genet A. 2006 Mar 1;140(5):537-9. PMID:16470795 doi:10.1002/ajmg.a.31106
- ↑ Miura K, Miura S, Yoshiura K, Seminara S, Hamaguchi D, Niikawa N, Masuzaki H. A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1. Hum Reprod. 2010 Apr;25(4):1076-80. doi: 10.1093/humrep/deq006. Epub 2010 Feb 6. PMID:20139426 doi:10.1093/humrep/deq006
- ↑ Kress W, Petersen B, Collmann H, Grimm T. An unusual FGFR1 mutation (fibroblast growth factor receptor 1 mutation) in a girl with non-syndromic trigonocephaly. Cytogenet Cell Genet. 2000;91(1-4):138-40. PMID:11173846
- ↑ Miura K, Miura S, Yoshiura K, Seminara S, Hamaguchi D, Niikawa N, Masuzaki H. A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1. Hum Reprod. 2010 Apr;25(4):1076-80. doi: 10.1093/humrep/deq006. Epub 2010 Feb 6. PMID:20139426 doi:10.1093/humrep/deq006
- ↑ . Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000 Nov;26(3):345-8. PMID:11062477 doi:10.1038/81664
- ↑ Bowe AE, Finnegan R, Jan de Beur SM, Cho J, Levine MA, Kumar R, Schiavi SC. FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate. Biochem Biophys Res Commun. 2001 Jun 22;284(4):977-81. PMID:11409890 doi:10.1006/bbrc.2001.5084
- ↑ Kato K, Jeanneau C, Tarp MA, Benet-Pages A, Lorenz-Depiereux B, Bennett EP, Mandel U, Strom TM, Clausen H. Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis. Secretion of fibroblast growth factor 23 requires O-glycosylation. J Biol Chem. 2006 Jul 7;281(27):18370-7. Epub 2006 Apr 25. PMID:16638743 doi:10.1074/jbc.M602469200
- ↑ Benet-Pages A, Orlik P, Strom TM, Lorenz-Depiereux B. An FGF23 missense mutation causes familial tumoral calcinosis with hyperphosphatemia. Hum Mol Genet. 2005 Feb 1;14(3):385-90. Epub 2004 Dec 8. PMID:15590700 doi:10.1093/hmg/ddi034
- ↑ Miura K, Miura S, Yoshiura K, Seminara S, Hamaguchi D, Niikawa N, Masuzaki H. A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1. Hum Reprod. 2010 Apr;25(4):1076-80. doi: 10.1093/humrep/deq006. Epub 2010 Feb 6. PMID:20139426 doi:10.1093/humrep/deq006
- ↑ Peters KG, Marie J, Wilson E, Ives HE, Escobedo J, Del Rosario M, Mirda D, Williams LT. Point mutation of an FGF receptor abolishes phosphatidylinositol turnover and Ca2+ flux but not mitogenesis. Nature. 1992 Aug 20;358(6388):678-81. PMID:1379697 doi:http://dx.doi.org/10.1038/358678a0
- ↑ Mohammadi M, Dionne CA, Li W, Li N, Spivak T, Honegger AM, Jaye M, Schlessinger J. Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis without affecting mitogenesis. Nature. 1992 Aug 20;358(6388):681-4. PMID:1379698 doi:http://dx.doi.org/10.1038/358681a0
- ↑ Mohammadi M, Dikic I, Sorokin A, Burgess WH, Jaye M, Schlessinger J. Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction. Mol Cell Biol. 1996 Mar;16(3):977-89. PMID:8622701
- ↑ Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M. Receptor specificity of the fibroblast growth factor family. J Biol Chem. 1996 Jun 21;271(25):15292-7. PMID:8663044
- ↑ Ong SH, Hadari YR, Gotoh N, Guy GR, Schlessinger J, Lax I. Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6074-9. Epub 2001 May 15. PMID:11353842 doi:10.1073/pnas.111114298
- ↑ Cross MJ, Lu L, Magnusson P, Nyqvist D, Holmqvist K, Welsh M, Claesson-Welsh L. The Shb adaptor protein binds to tyrosine 766 in the FGFR-1 and regulates the Ras/MEK/MAPK pathway via FRS2 phosphorylation in endothelial cells. Mol Biol Cell. 2002 Aug;13(8):2881-93. PMID:12181353 doi:10.1091/mbc.E02-02-0103
- ↑ Hu Y, Fang X, Dunham SM, Prada C, Stachowiak EK, Stachowiak MK. 90-kDa ribosomal S6 kinase is a direct target for the nuclear fibroblast growth factor receptor 1 (FGFR1): role in FGFR1 signaling. J Biol Chem. 2004 Jul 9;279(28):29325-35. Epub 2004 Apr 26. PMID:15117958 doi:10.1074/jbc.M311144200
- ↑ Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, Ornitz DM. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem. 2006 Jun 9;281(23):15694-700. Epub 2006 Apr 4. PMID:16597617 doi:10.1074/jbc.M601252200
- ↑ Kurosu H, Choi M, Ogawa Y, Dickson AS, Goetz R, Eliseenkova AV, Mohammadi M, Rosenblatt KP, Kliewer SA, Kuro-o M. Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem. 2007 Sep 14;282(37):26687-95. Epub 2007 Jul 10. PMID:17623664 doi:10.1074/jbc.M704165200
- ↑ Citores L, Bai L, Sorensen V, Olsnes S. Fibroblast growth factor receptor-induced phosphorylation of STAT1 at the Golgi apparatus without translocation to the nucleus. J Cell Physiol. 2007 Jul;212(1):148-56. PMID:17311277 doi:10.1002/jcp.21014
- ↑ Haugsten EM, Malecki J, Bjorklund SM, Olsnes S, Wesche J. Ubiquitination of fibroblast growth factor receptor 1 is required for its intracellular sorting but not for its endocytosis. Mol Biol Cell. 2008 Aug;19(8):3390-403. doi: 10.1091/mbc.E07-12-1219. Epub 2008, May 14. PMID:18480409 doi:10.1091/mbc.E07-12-1219
- ↑ Dunham-Ems SM, Lee YW, Stachowiak EK, Pudavar H, Claus P, Prasad PN, Stachowiak MK. Fibroblast growth factor receptor-1 (FGFR1) nuclear dynamics reveal a novel mechanism in transcription control. Mol Biol Cell. 2009 May;20(9):2401-12. doi: 10.1091/mbc.E08-06-0600. Epub 2009, Mar 4. PMID:19261810 doi:10.1091/mbc.E08-06-0600
- ↑ Lew ED, Furdui CM, Anderson KS, Schlessinger J. The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutations. Sci Signal. 2009 Feb 17;2(58):ra6. doi: 10.1126/scisignal.2000021. PMID:19224897 doi:10.1126/scisignal.2000021
- ↑ Persaud A, Alberts P, Hayes M, Guettler S, Clarke I, Sicheri F, Dirks P, Ciruna B, Rotin D. Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function. EMBO J. 2011 Jul 15;30(16):3259-73. doi: 10.1038/emboj.2011.234. PMID:21765395 doi:10.1038/emboj.2011.234
- ↑ Plotnikov AN, Hubbard SR, Schlessinger J, Mohammadi M. Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity. Cell. 2000 May 12;101(4):413-24. PMID:10830168
- ↑ Bae JH, Lew ED, Yuzawa S, Tome F, Lax I, Schlessinger J. The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site. Cell. 2009 Aug 7;138(3):514-24. PMID:19665973 doi:S0092-8674(09)00631-X
- ↑ Bae JH, Boggon TJ, Tome F, Mandiyan V, Lax I, Schlessinger J. Asymmetric receptor contact is required for tyrosine autophosphorylation of fibroblast growth factor receptor in living cells. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2866-71. Epub 2010 Jan 26. PMID:20133753
- ↑ . Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000 Nov;26(3):345-8. PMID:11062477 doi:10.1038/81664
- ↑ Bowe AE, Finnegan R, Jan de Beur SM, Cho J, Levine MA, Kumar R, Schiavi SC. FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate. Biochem Biophys Res Commun. 2001 Jun 22;284(4):977-81. PMID:11409890 doi:10.1006/bbrc.2001.5084
- ↑ Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S, Yamashita T. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res. 2004 Mar;19(3):429-35. Epub 2003 Dec 29. PMID:15040831 doi:10.1359/JBMR.0301264
- ↑ Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, Ornitz DM. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem. 2006 Jun 9;281(23):15694-700. Epub 2006 Apr 4. PMID:16597617 doi:10.1074/jbc.M601252200
- ↑ Wang H, Yoshiko Y, Yamamoto R, Minamizaki T, Kozai K, Tanne K, Aubin JE, Maeda N. Overexpression of fibroblast growth factor 23 suppresses osteoblast differentiation and matrix mineralization in vitro. J Bone Miner Res. 2008 Jun;23(6):939-48. doi: 10.1359/jbmr.080220. PMID:18282132 doi:10.1359/jbmr.080220
- ↑ Chen G, Liu Y, Goetz R, Fu L, Jayaraman S, Hu MC, Moe OW, Liang G, Li X, Mohammadi M. alpha-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling. Nature. 2018 Jan 25;553(7689):461-466. doi: 10.1038/nature25451. Epub 2018 Jan, 17. PMID:29342138 doi:http://dx.doi.org/10.1038/nature25451
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