Receptor tyrosine kinases positively regulate BACE activity and Amyloid-beta production through enhancing BACE internalization
文献类型：期刊论文
| 作者 | Zou, L; Wang, Z; Shen, L; Bao, GB; Wang, T; Kang, JH; Pei, G |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2007 |
| 卷号 | 17期号:5页码:389-401 |
| 关键词 | beta-site APP cleavage enzyme RTK Amyloid-beta Src |
| 通讯作者 | Pei, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Lab Mol Cell Biol, Shanghai 200031, Peoples R China.,gpei@sibs.ac.cn |
| 英文摘要 | Amyloid-beta (A beta) peptide, the primary constituent of senile plaques in Alzheimer's disease (AD), is generated by beta-secretase- and gamma-secretase-mediated sequential proteolysis of the amyloid precursor protein (APP). The aspartic protease, beta -site APP cleavage enzyme (BACE), has been identified as the main beta-secretase in brain but the regulation of its activity is largely unclear. Here, we demonstrate that both BACE activity and subsequent A beta production are enhanced after stimulation of receptor tyrosine kinases (RTKs), such as the receptors for epidermal growth factor (EGF) and nerve growth factor (NGF), in cultured cells as well as in mouse hippocampus. Furthermore, stimulation of RTKs also induces BACE internalization into endosomes and Golgi apparatus. This enhancement of BACE activity and A beta production upon RTK activation could be specifically inhibited by Src family kinase inhibitors and by depletion of endogenous c-Src with RNAi, and could be mimicked by over-expressed c-Src. Moreover, blockage of BACE internalization by a dominant negative form of Rab5 also abolished the enhancement of BACE activity and A beta production, indicating the requirement of BACE internalization for the enhanced activity. Taken together, our study presents evidence that BACE activity and A beta production are under the regulation of RTKs and this is achieved via RTK-stimulated BACE internalization, and suggests that an aberration of such regulation might contribute to pathogenic A beta production. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | EPIDERMAL-GROWTH-FACTOR ; PROTEIN-CLEAVING ENZYME ; PRECURSOR PROTEIN ; ALZHEIMERS-DISEASE ; A-BETA ; C-SRC ; SECRETASE ACTIVITY ; SORTING SIGNAL ; PC12 CELLS ; ENDOCYTOSIS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000247525700003 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1567]  |
| 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 | Zou, L,Wang, Z,Shen, L,et al. Receptor tyrosine kinases positively regulate BACE activity and Amyloid-beta production through enhancing BACE internalization[J]. CELL RESEARCH,2007,17(5):389-401. |
| APA | Zou, L.,Wang, Z.,Shen, L.,Bao, GB.,Wang, T.,...&Pei, G.(2007).Receptor tyrosine kinases positively regulate BACE activity and Amyloid-beta production through enhancing BACE internalization.CELL RESEARCH,17(5),389-401. |
| MLA | Zou, L,et al."Receptor tyrosine kinases positively regulate BACE activity and Amyloid-beta production through enhancing BACE internalization".CELL RESEARCH 17.5(2007):389-401. |
入库方式： OAI收割
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。