Extensive Crosstalk between O-GlcNAcylation and Phosphorylation Regulates Akt Signaling
文献类型：期刊论文
| 作者 | Wang, Shuai2; Huang, Xun2 ; Sun, Danni2; Xin, Xianliang2; Pan, Qiuming2; Peng, Shuying3; Liang, Zhongjie1; Luo, Cheng1; Yang, Yiming3; Jiang, Hualiang1
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| 刊名 | PLOS ONE
 |
| 出版日期 | 2012-05-22 |
| 卷号 | 7期号:5 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0037427 |
| 文献子类 | Article |
| 英文摘要 | O-linked N-acetylglucosamine glycosylations (O-GlcNAc) and O-linked phosphorylations (O-phosphate), as two important types of post-translational modifications, often occur on the same protein and bear a reciprocal relationship. In addition to the well documented phosphorylations that control Akt activity, Akt also undergoes O-GlcNAcylation, but the interplay between these two modifications and the biological significance remain unclear, largely due to the technique challenges. Here, we applied a two-step analytic approach composed of the O-GlcNAc immunoenrichment and subsequent O-phosphate immunodetection. Such an easy method enabled us to visualize endogenous glycosylated and phosphorylated Akt subpopulations in parallel and observed the inhibitory effect of Akt O-GlcNAcylations on its phosphorylation. Further studies utilizing mass spectrometry and mutagenesis approaches showed that O-GlcNAcylations at Thr 305 and Thr 312 inhibited Akt phosphorylation at Thr 308 via disrupting the interaction between Akt and PDK1. The impaired Akt activation in turn resulted in the compromised biological functions of Akt, as evidenced by suppressed cell proliferation and migration capabilities. Together, this study revealed an extensive crosstalk between O-GlcNAcylations and phosphorylations of Akt and demonstrated O-GlcNAcylation as a new regulatory modification for Akt signaling. |
| WOS关键词 | BETA-N-ACETYLGLUCOSAMINE ; INDUCE INSULIN-RESISTANCE ; PROTEIN-KINASE B ; POSTTRANSLATIONAL MODIFICATIONS ; 3T3-L1 ADIPOCYTES ; IN-VIVO ; GLCNAC ; ACTIVATION ; UBIQUITINATION ; IDENTIFICATION |
| 资助项目 | Natural Science Foundation of China for Distinguished Young Scholars[30725046] ; Natural Science Foundation of China for Innovation Research Group[81021062] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000305345300039 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278073]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Wang, Shuai |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Discovery & Design, State Key Lab Drug Res, Shanghai 200031, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 200031, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Mass Spectrometry, Shanghai 200031, Peoples R China; 4.Imperial Coll London, Glycosci Lab, Fac Med, Harrow, Middx, England |
| 推荐引用方式 GB/T 7714 | Wang, Shuai,Huang, Xun,Sun, Danni,et al. Extensive Crosstalk between O-GlcNAcylation and Phosphorylation Regulates Akt Signaling[J]. PLOS ONE,2012,7(5). |
| APA | Wang, Shuai.,Huang, Xun.,Sun, Danni.,Xin, Xianliang.,Pan, Qiuming.,...&Geng, Meiyu.(2012).Extensive Crosstalk between O-GlcNAcylation and Phosphorylation Regulates Akt Signaling.PLOS ONE,7(5). |
| MLA | Wang, Shuai,et al."Extensive Crosstalk between O-GlcNAcylation and Phosphorylation Regulates Akt Signaling".PLOS ONE 7.5(2012). |
入库方式： OAI收割
来源：上海药物研究所
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