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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, Ting1; Shao, Mengle1; Qiu, Yifu1; Huang, Jialiang3,4,6; Zhang, Yongliang1; Song, Bo1; Wang, Qiong1; Jiang, Lei1; Liu, Yi1; Han, Jing-Dong J.3,4,6
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版日期2011-09-20
卷号108期号:38页码:15852-15857
关键词endoplasmic reticulum stress G protein-coupled receptor metabolic disease
ISSN号0027-8424
DOI10.1073/pnas.1107394108
文献子类Article
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.
WOS关键词UNFOLDED PROTEIN RESPONSE ; ENDOPLASMIC-RETICULUM STRESS ; PANCREATIC BETA-CELLS ; ER STRESS ; MESSENGER-RNA ; TRANSMEMBRANE PROTEIN ; TRANSCRIPTION FACTOR ; KINASE ACTIVATION ; IRE1 ; HOMEOSTASIS
资助项目National Natural Science Foundation[81021002] ; National Natural Science Foundation[30988002] ; National Natural Science Foundation[90713027] ; National Natural Science Foundation[30830033] ; National Natural Science Foundation[30970584] ; Ministry of Science and Technology[2011CB910900] ; Ministry of Science and Technology[2007CB947100] ; Ministry of Science and Technology[2006BAI23B00] ; Chinese Academy of Sciences[KSCX2-EW-R-09] ; Chinese Academy of Sciences[KSCX1-YW-02] ; Chief Scientist Program[SIBS2008006] ; Chinese Academy of Sciences/State Administration of Foreign Experts Affairs[00000000] ; Science and Technology Commission of Shanghai Municipality[10XD1406400] ; Science and Technology Commission of Shanghai Municipality[08dj1400601]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000295030000041
出版者NATL ACAD SCIENCES
源URL[http://119.78.100.183/handle/2S10ELR8/278399]  
专题国家新药筛选中心
药物安全性评价中心
通讯作者Liu, Yong
作者单位1.Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Max Planck Partner Inst Computat Biol, Shanghai 200031, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China;
3.Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China;
4.Chinese Acad Sci, Max Planck Partner Inst Computat Biol, Key Lab Computat Biol, Shanghai 200031, Peoples R China;
5.Nanjing Univ, Model Anim Res Ctr, Nanjing 210093, Peoples R China;
6.Chinese Acad Sci, Inst Genet & Dev Biol, Beijing 100101, Peoples R China;
7.Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA
8.Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA;
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：上海药物研究所

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