Structural insights into regulatory mechanisms of MO25-mediated kinase activation
文献类型：期刊论文
| 作者 | Hao, Q; Feng, M; Shi, ZB; Li, CC; Chen, M; Wang, WJ; Zhang, M; Jiao, S; Zhou, ZC |
| 刊名 | JOURNAL OF STRUCTURAL BIOLOGY
 |
| 出版日期 | 2014 |
| 卷号 | 186期号:2页码:224-233 |
| 关键词 | MO25 Germinal center kinases alpha C helix Activation-loop Lysine-glutamate ion pair |
| 通讯作者 | Zhou, ZC (reprint author), Chinese Acad Sci, SIBS, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,zczhou@sibcb.ac.cn |
| 英文摘要 | The tumor suppressor kinase LKB1 and germinal center kinases (GCKs) are key regulators of various cellular functions. The adaptor molecule MO25 not only recruits and activates LKBI through the pseudokinase STRAD, but also may directly activate GCKs like MST3, MST4, STK25, OSRI and SPAK. Targeting MO25 in a pathological setting has been recently studied in mouse. Yet the regulatory mechanism of MO25-mediated kinase activation is not fully understood. Here, our structural studies of MO25-related kinases reveal that MO25 binds to and activates GCK kinases or pseudokinase through a unified structural mechanism, featuring an active conformation of the alpha C helix and A-loop stabilized by MO25. Compared to GCKs that are directly activated by MO25-binding, activation of LKB1 has evolved additional layer of regulatory machinery, i.e., MO25 "activates" the pseudokinase STRAD, which in turn activates LKBI. Importantly, the structures of MO25 alpha-STK25 and MO25 alpha-MST3 determined in this work represent a transition/intermediate state and a fully activated state, respectively during the MO25-mediated kinase activating process. (C) 2014 Elsevier Inc. All rights reserved. |
| 学科主题 | Biochemistry & Molecular Biology; Biophysics; Cell Biology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
| 关键词[WOS] | CRYSTAL-STRUCTURE ; PROTEIN-KINASES ; STE20-LIKE KINASE ; COMPLEX ; MST3 ; MO25 ; LKB1 ; POLARIZATION ; DOMAIN ; STRAD |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000335705700003 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/141]  |
| 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 | Hao, Q,Feng, M,Shi, ZB,et al. Structural insights into regulatory mechanisms of MO25-mediated kinase activation[J]. JOURNAL OF STRUCTURAL BIOLOGY,2014,186(2):224-233. |
| APA | Hao, Q.,Feng, M.,Shi, ZB.,Li, CC.,Chen, M.,...&Zhou, ZC.(2014).Structural insights into regulatory mechanisms of MO25-mediated kinase activation.JOURNAL OF STRUCTURAL BIOLOGY,186(2),224-233. |
| MLA | Hao, Q,et al."Structural insights into regulatory mechanisms of MO25-mediated kinase activation".JOURNAL OF STRUCTURAL BIOLOGY 186.2(2014):224-233. |
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