LKB1 regulates TCR-mediated PLC gamma 1 activation and thymocyte positive selection
文献类型：期刊论文
| 作者 | Cao, YH; Li, H; Liu, HF; Zhang, M; Hua, ZC; Ji, HB; Liu, XL |
| 刊名 | EMBO JOURNAL
 |
| 出版日期 | 2011 |
| 卷号 | 30期号:10页码:2083-2093 |
| 关键词 | LKB1 PLC gamma 1 positive selection TCR signalling thymocyte |
| 通讯作者 | Liu, XL (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,liux@sibs.ac.cn |
| 英文摘要 | The serine/threonine kinase LKB1 is a tumour suppressor that regulates cell growth, polarity, and proliferation in many different cell types. We previously demonstrated that LKB1 controls thymocyte survival via regulation of AMPK activation. In this study, we show that LKB1 was also involved in thymocyte positive selection through regulation of T cell receptor (TCR) signalling. Both LckCre- and CD4-Cre-mediated deletion of LKB1 impaired the generation of mature CD4 and CD8 single positive (SP) thymocytes that might have resulted from the attenuated tyrosine phosphorylation of phospholipase C-gamma 1 (PLC gamma 1) in the absence of LKB1. We found that LKB1 was directly phosphorylated by Lck at tyrosine residues 36, 261, and 365 and predominately interacted with LAT and PLC gamma 1 following TCR stimulation. Loss of LKB1 led to impaired recruitment of PLC gamma 1 to the LAT signalosome. Correlatively, LKB1-deficient thymocytes failed to upregulate lineage-specifying factors, and to differentiate into SP thymocytes even if their impaired survival was rescued. These observations indicated that LKB1 is a critical component involved in TCR signalling, and our studies provide novel insights into the mechanisms of LKB1-mediated thymocyte development. The EMBO Journal (2011) 30, 2083-2093. doi: 10.1038/emboj.2011.116; Published online 12 April 2011 |
| 学科主题 | Biochemistry & Molecular Biology; Cell Biology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Cell Biology |
| 关键词[WOS] | T-CELL DEVELOPMENT ; JEGHERS CANCER SYNDROME ; PROTEIN-KINASE ; PHOSPHOLIPASE C-GAMMA-1 ; DEPENDENT REGULATION ; NEGATIVE SELECTION ; RUNX PROTEINS ; IN-VITRO ; KAPPA-B ; RECEPTOR |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000291645400021 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/861]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Cao, YH,Li, H,Liu, HF,et al. LKB1 regulates TCR-mediated PLC gamma 1 activation and thymocyte positive selection[J]. EMBO JOURNAL,2011,30(10):2083-2093. |
| APA | Cao, YH.,Li, H.,Liu, HF.,Zhang, M.,Hua, ZC.,...&Liu, XL.(2011).LKB1 regulates TCR-mediated PLC gamma 1 activation and thymocyte positive selection.EMBO JOURNAL,30(10),2083-2093. |
| MLA | Cao, YH,et al."LKB1 regulates TCR-mediated PLC gamma 1 activation and thymocyte positive selection".EMBO JOURNAL 30.10(2011):2083-2093. |
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