| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○著者 (必須): | 1. | 髙士 祐一
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| 2. | 小迫 英尊 ([徳島大学.先端酵素学研究所.基幹研究部門])
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| 3. | 沢津橋 俊 ([徳島大学.先端酵素学研究所.技術開発支援部門])
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| 4. | (英) Kinoshita Yuka (日) 木下 祐加 (読) きのした ゆか
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| 5. | (英) Ito Nobuaki (日) 伊東 伸朗 (読) いとう のぶあき
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| 6. | (英) Tsoumpra K. Maria (日) (読)
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| 7. | (英) Nangaku Masaomi (日) 南学 正臣 (読) なんがく まさおみ
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| 8. | 安倍 正博
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| 9. | 松久 宗英 ([徳島大学.先端酵素学研究所.基幹研究部門]/徳島大学病院アンチエイジングセンター センター長(併任))
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| 10. | (英) Kato Shigeaki (日) 加藤 茂明 (読) かとう しげあき
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| 11. | 松本 俊夫
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| 12. | 福本 誠二
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| ○題名 (必須): | □ | (英) Activation of unliganded FGF receptor by extracellular phosphate potentiates proteolytic protection of FGF23 by its O-glycosylation (日)
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| ○要約 (任意): | □ | (英) Fibroblast growth factor (FGF) 23 produced by bone is a hormone that decreases serum phosphate (Pi). Reflecting its central role in Pi control, serum FGF23 is tightly regulated by serum Pi alterations. FGF23 levels are regulated by the transcriptional event and posttranslational cleavage into inactive fragments before its secretion. For the latter, O-glycosylation of FGF23 by gene product prevents the cleavage, leading to an increase in serum FGF23. However, the molecular basis of Pi sensing in the regulation of serum FGF23 remains elusive. In this study, we showed that high Pi diet enhanced the skeletal expression of , but not , with expected increases in serum FGF23 and Pi in mice. induction by high Pi was further observed in osteoblastic UMR 106 cells, and this was mediated by activation of the extracellular signal-regulated kinase (ERK) pathway. Through proteomic searches for the upstream sensor for high Pi, we identified one subtype of the FGF receptor (FGFR1c), which was phosphorylated by high Pi in the absence of FGFs. The mode of unliganded FGFR activation by high Pi appeared different from that of FGFR bound to a canonical FGFR ligand (FGF2) when phosphorylation of the FGFR substrate 2α and ERK was monitored. Finally, we showed that an FGFR inhibitor and conditional deletion of in osteoblasts/osteocytes abrogated high Pi diet-induced increases in serum FGF23 and femoral expression in mice. Thus, these findings uncover an unrecognized facet of unliganded FGFR function and illustrate a Pi-sensing pathway involved in regulation of FGF23 production. (日)
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| ○キーワード (推奨): |
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| ○誌名 (必須): | □ | Proceedings of the National Academy of Sciences of the United States of America ([The National Academy of Sciences of the United States of America])
(pISSN: 0027-8424, eISSN: 1091-6490)
| ○ISSN (任意): | □ | 1091-6490
ISSN: 0027-8424
(pISSN: 0027-8424, eISSN: 1091-6490) Title: Proceedings of the National Academy of Sciences of the United States of AmericaTitle(ISO): Proc Natl Acad Sci U S APublisher: National Academy of Sciences (NLM Catalog)
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(CrossRef)
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| ○巻 (必須): | □ | 116
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| ○号 (必須): | □ | 23
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| ○頁 (必須): | □ | 11418 11427
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2019年 5月 16日 (令和 元年 5月 16日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1073/pnas.1815166116 (→Scopusで検索)
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| ○PMID (任意): | □ | 31097591 (→Scopusで検索)
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| ○備考 (任意): | 1. | (英) Article.ELocationID: 201815166 (日)
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| 2. | (英) Article.ELocationID: 10.1073/pnas.1815166116 (日)
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| 3. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 4. | (英) KeywordList.Keyword: fibroblast growth factor 23 (日)
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| 5. | (英) KeywordList.Keyword: fibroblast growth factor receptor 1 (日)
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| 6. | (英) KeywordList.Keyword: phosphate sensor (日)
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| 7. | (英) CoiStatement: The authors declare no conflict of interest. (日)
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