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PKA phosphorylation couples hepatic inositol-requiring enzyme 1 alpha to glucagon signaling in glucose metabolism
文献类型：期刊论文
| 作者 | Mao, Ting; Shao, Mengle; Qiu, Yifu; Huang, Jialiang; Zhang, Yongliang; Song, Bo; Wang, Qiong; Jiang, Lei; Liu, Yi（刘浥）; Han, Jing-Dong J. |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 2011 |
| 卷号 | 108期号:38页码:15852-15857 |
| 关键词 | endoplasmic reticulum stress G protein-coupled receptor metabolic disease |
| 通讯作者 | Liu, Y (reprint author), Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Max Planck Partner Inst Computat Biol, Shanghai 200031, Peoples R China. |
| 英文摘要 | The endoplasmic reticulum (ER)-resident protein kinase/endoribo-nuclease inositol-requiring enzyme 1 (IRE1) is activated through transautophosphorylation in response to protein folding overload in the ER lumen and maintains ER homeostasis by triggering a key branch of the unfolded protein response. Here we show that mammalian IRE1 alpha in liver cells is also phosphorylated by a kinase other than itself in response to metabolic stimuli. Glucagon-stimulated protein kinase PKA, which in turn phosphorylated IRE1 alpha at Ser(724), a highly conserved site within the kinase activation domain. Blocking Ser(724) phosphorylation impaired the ability of IRE1 alpha to augment the up-regulation by glucagon signaling of the expression of gluconeogenic genes. Moreover, hepatic IRE1 alpha was highly phosphorylated at Ser(724) by PKA in mice with obesity, and silencing hepatic IRE1 alpha markedly reduced hyperglycemia and glucose intolerance. Hence, these results suggest that IRE1 alpha integrates signals from both the ER lumen and the cytoplasm in the liver and is coupled to the glucagon signaling in the regulation of glucose metabolism. |
| 类目[WOS] | Multidisciplinary Sciences |
| 研究领域[WOS] | Science & Technology - Other Topics |
| 关键词[WOS] | UNFOLDED PROTEIN RESPONSE ; ENDOPLASMIC-RETICULUM STRESS ; PANCREATIC BETA-CELLS ; ER STRESS ; MESSENGER-RNA ; TRANSMEMBRANE PROTEIN ; TRANSCRIPTION FACTOR ; KINASE ACTIVATION ; IRE1 ; HOMEOSTASIS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000295030000041 |
| 公开日期 | 2015-12-24 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/286]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_糖脂代谢与调控研究组 |
| 推荐引用方式 GB/T 7714 | Mao, Ting,Shao, Mengle,Qiu, Yifu,et al. PKA phosphorylation couples hepatic inositol-requiring enzyme 1 alpha to glucagon signaling in glucose metabolism[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2011,108(38):15852-15857. |
| APA | Mao, Ting.,Shao, Mengle.,Qiu, Yifu.,Huang, Jialiang.,Zhang, Yongliang.,...&Liu, Yong.(2011).PKA phosphorylation couples hepatic inositol-requiring enzyme 1 alpha to glucagon signaling in glucose metabolism.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,108(38),15852-15857. |
| MLA | Mao, Ting,et al."PKA phosphorylation couples hepatic inositol-requiring enzyme 1 alpha to glucagon signaling in glucose metabolism".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 108.38(2011):15852-15857. |
入库方式： OAI收割
来源：上海营养与健康研究所
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