Abstract:
:Fibroblast growth factor 23 (FGF23) is a phosphotropic hormone that belongs to a subfamily of endocrine FGFs with evolutionarily conserved functions in C. elegans and fruit flies. FAM20C phosphorylates FGF23 post-translationally, targeting to proteolysis through subtilisin-like proprotein convertase FURIN, resulting in secretion of FGF23 fragments. O-glycosylation of FGF23 through GALNT3 appears to prevent proteolysis, resulting in secretion of biologically active intact FGF23. In the circulation, FGF23 may undergo further processing by plasminogen activators. Crystal structures show the ectodomain of the cognate FGF23 receptor FGFR1c binds with the ectodomain of the co-receptor alpha-KLOTHO. The KLOTHO-FGFR1c double heterodimer creates a high-affinity binding site for the FGF23 C-terminus. The topology of FGF23 deviates from that of paracrine FGFs, resulting in poor affinity for heparan sulfate, which may explain why FGF23 diffuses freely in the bone matrix to enter the bloodstream following its secretion by cells of osteoblastic lineage. Intact FGF23 signalling by this canonical pathway activates FRS2/RAS/RAF/MEK/ERK1/2. It reduces serum phosphate by inhibiting 1,25-Dihydroxyvitamin D synthesis, suppressing intestinal phosphate absorption, and by downregulating the transporters NPT2a and NPT2c, suppressing phosphate reabsorption in the proximal tubules. The physiological role of FGF23 fragments, which may be inhibitory, remains unclear. Pharmacological and genetic activation of canonical FGF23 signalling causes hypophosphatemic disorders, while its inhibition results in hyperphosphatemic disorders. Non-canonical FGF23 signalling through binding and activation of FGFR3/FGFR4/calcineurin/NFAT in an alpha-KLOTHO-independent fashion mainly occurs at extremely elevated circulating FGF23 levels and may contribute to mortality due to cardiovascular disease and left ventricular hypertrophy in chronic kidney disease.
journal_name
J Mol Endocrinoljournal_title
Journal of molecular endocrinologyauthors
Ho BB,Bergwitz Cdoi
10.1530/JME-20-0178subject
Has Abstractpub_date
2020-12-01 00:00:00eissn
0952-5041issn
1479-6813pii
JME-20-0178.R1pub_type
杂志文章,评审abstract::The peroxisome proliferator-activated receptor (PPAR) is a member of the steroid hormone receptor superfamily and is activated by a variety of fibrate hypolipidaemic drugs and non-genotoxic rodent hepatocarcinogens that are collectively termed peroxisome proliferators. A key marker of peroxisome proliferator action is...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0110037
更新日期:1993-08-01 00:00:00
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journal_title:Journal of molecular endocrinology
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doi:10.1677/jme.0.0080079
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0040135
更新日期:1990-04-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0320437
更新日期:2004-04-01 00:00:00
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journal_title:Journal of molecular endocrinology
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-14-0213
更新日期:2015-02-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
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更新日期:2012-10-30 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-16-0223
更新日期:2017-10-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-11-0189
更新日期:2012-07-26 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-13-0015
更新日期:2014-01-30 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0180137
更新日期:1997-04-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-08-0068
更新日期:2009-02-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-19-0183
更新日期:2019-11-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0300049
更新日期:2003-02-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-12-0200
更新日期:2013-06-04 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.01588
更新日期:2004-12-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 历史文章,杂志文章
doi:10.1677/jme.0.0260011
更新日期:2001-02-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1530/JME-13-0220
更新日期:2013-12-19 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
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更新日期:2011-03-03 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
doi:10.1677/jme.0.0260079
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0270145
更新日期:2001-10-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-15-0224
更新日期:2016-02-01 00:00:00
abstract::1,25-(OH)2-Vitamin D3 (1,25-D3) and the thyroid hormone tri-iodothyronine (T3) were previously shown to behave as adipogenic agents in murine Ob17 preadipocytes. Moreover, these agents interfere with each other's action during adipocyte differentiation. T3 receptor (TR) expression and a downmodulation of T3 binding si...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.1.01572
更新日期:2005-02-01 00:00:00
abstract::Orexin-A and -B are known to stimulate food intake in mammals. However, the critical roles of orexins in birds are not fully understood, since orexins have no stimulatory effect on food intake in the chicken. To understand the physiological role(s) of orexins in birds, we have cloned chicken orexin receptor (cOXR) cDN...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0310499
更新日期:2003-12-01 00:00:00
abstract::The p160 coactivators, steroid receptor coactivator-1 (SRC-1), transcriptional intermediary factor-2 (TIF2) and receptor-associated coactivator-3 (RAC3), as well as the coactivator/integrator CBP, mediate estrogen receptor-alpha (ERalpha)-dependent gene expression. Although these coactivators are widely expressed, ERa...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0320307
更新日期:2004-02-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-09-0048
更新日期:2010-01-01 00:00:00
abstract::We used the Crm1 inhibitor leptomycin B (LMB) to examine a possible involvement of nuclear export in estrogen receptor alpha (ER) level and function in MCF-7 breast carcinoma cells. As revealed by immunofluorescence microscopy and western blotting with anti-ER antibodies, LMB produced an accumulation of ER in cell nuc...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/JME-07-0040
更新日期:2007-08-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
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更新日期:2019-04-01 00:00:00
abstract::Cytochrome P450 21-hydroxylase (P450c21) is a key enzyme for corticosteroidogenesis. To understand the regulatory mechanisms of cortisol production in fish, we have cloned a cDNA encoding P450c21, for the first time in non-mammalian vertebrates, from the head kidney of the eel (Anguilla japonica). The overall similari...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0310327
更新日期:2003-10-01 00:00:00
abstract::Differences in binding and structural properties of ovine testicular FSH and LH receptors were investigated. The ovine FSH receptor did not discriminate between FSH of different species, although equine FSH was more reactive. In the same tissue, however, the LH receptor showed marked preference for ovine and bovine LH...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0060291
更新日期:1991-06-01 00:00:00