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DOI | 10.1038/s41467-019-09742-5 |
Postprandial FGF19-induced phosphorylation by Src is critical for FXR function in bile acid homeostasis | |
Byun, Sangwon1; Kim, Dong-Hyun1; Ryerson, Daniel1; Kim, Young-Chae1; Sun, Hao1; Kong, Bo2; Yau, Peter3; Guo, Grace2; Xu, H. Eric4; Kemper, Byron1; Kemper, Jongsook Kim1 | |
2019-04-29 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Farnesoid-X-Receptor (FXR) plays a central role in maintaining bile acid (BA) homeostasis by transcriptional control of numerous enterohepatic genes, including intestinal FGF19, a hormone that strongly represses hepatic BA synthesis. How activation of the FGF19 receptor at the membrane is transmitted to the nucleus for transcriptional regulation of BA levels and whether FGF19 signaling posttranslationally modulates FXR function remain largely unknown. Here we show that FXR is phosphorylated at Y67 by non-receptor tyrosine kinase, Src, in response to postprandial FGF19, which is critical for its nuclear localization and transcriptional regulation of BA levels. Liver-specific expression of phospho-defective Y67F-FXR or Src downregulation in mice results in impaired homeostatic responses to acute BA feeding, and exacerbates cholestatic pathologies upon drug-induced hepatobiliary insults. Also, the hepatic FGF19-Src-FXR pathway is defective in primary biliary cirrhosis (PBC) patients. This study identifies Src-mediated FXR phosphorylation as a potential therapeutic target and biomarker for BA-related enterohepatic diseases. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000437102100001 |
WOS关键词 | SMALL HETERODIMER PARTNER ; FARNESOID X RECEPTOR ; GROWTH-FACTOR 19 ; NUCLEAR RECEPTORS ; METABOLISM ; EXPRESSION ; AUTOPHAGY ; DISEASE ; MICE ; CHOLESTASIS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204344 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA; 2.Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharmacol & Toxicol, Piscataway, NJ 08854 USA; 3.Univ Illinois, Prote Ctr, Urbana, IL 61801 USA; 4.Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA |
推荐引用方式 GB/T 7714 | Byun, Sangwon,Kim, Dong-Hyun,Ryerson, Daniel,et al. Postprandial FGF19-induced phosphorylation by Src is critical for FXR function in bile acid homeostasis[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Byun, Sangwon.,Kim, Dong-Hyun.,Ryerson, Daniel.,Kim, Young-Chae.,Sun, Hao.,...&Kemper, Jongsook Kim.(2019).Postprandial FGF19-induced phosphorylation by Src is critical for FXR function in bile acid homeostasis.NATURE COMMUNICATIONS,9. |
MLA | Byun, Sangwon,et al."Postprandial FGF19-induced phosphorylation by Src is critical for FXR function in bile acid homeostasis".NATURE COMMUNICATIONS 9(2019). |
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