Vav2 is a novel APP-interacting protein that regulates APP protein level
文献类型：期刊论文
| 作者 | Zhang, Youjia6,7; Yang, Xiaxin4,5; Liu, Yongrui6; Ge, Liang7; Wang, Jiarong7 ; Sun, Xiulian2,3,4; Wu, Bo7; Wang, Junfeng1,6,7
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| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2022-07-26 |
| 卷号 | 12 |
| ISSN号 | 2045-2322 |
| DOI | 10.1038/s41598-022-16883-z |
| 通讯作者 | Sun, Xiulian(xiulians@gmail.com) ; Wu, Bo(wubo@hmfl.ac.cn) ; Wang, Junfeng(junfeng@hmfl.ac.cn) |
| 英文摘要 | Amyloid precursor protein (APP) is a transmembrane protein that plays critical role in the pathogenesis of Alzheimer's disease (AD). It is also involved in many types of cancers. Increasing evidence has shown that the tyrosine phosphorylation site Y682 in the intracellular tail of APP is crucial for APP function. Here, we report that Vav2, a guanine nucleotide exchange factor (GEF) for Rho family GTPase, is a novel interaction partner of APP. We found that Vav2-SH2 domain was able to bind directly to the Y682-phosphorylated intracellular tail of APP through isothermal titration calorimetry and NMR titrating experiments. The crystal structure of Vav2-SH2 in complex with an APP-derived phosphopeptide was determined to understand the structural basis of this recognition specificity. The interaction of APP and Vav2 in a full-length manner was further confirmed in cells by GST pull-down, co-immunoprecipitation and immunofluorescence staining experiments. In addition, we found overexpression of Vav2 could inhibit APP degradation and markedly increase the protein levels of APP and its cleavage productions in 20E2 cells, and this function of Vav2 required a functional SH2 domain. |
| WOS关键词 | AMYLOID PRECURSOR PROTEIN ; NUCLEOTIDE EXCHANGE FACTOR ; A-BETA-PP ; ALZHEIMERS-DISEASE ; STRUCTURAL BASIS ; FAMILY ; PHOSPHORYLATION ; BINDING ; FE65 ; IDENTIFICATION |
| 资助项目 | National Natural Science Foundation of China[21673244] ; National Natural Science Foundation of China[91849130] ; Foundation of Anhui Technologies Major Program[201903a07020026] ; Collaborative Innovation Program of Hefei Science Center, CAS[2020HSC-CIP008] ; High Magnetic Field Laboratory of Anhui Province |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000835004100047 |
| 出版者 | NATURE PORTFOLIO |
| 资助机构 | National Natural Science Foundation of China ; Foundation of Anhui Technologies Major Program ; Collaborative Innovation Program of Hefei Science Center, CAS ; High Magnetic Field Laboratory of Anhui Province |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/132189]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Sun, Xiulian; Wu, Bo; Wang, Junfeng |
| 作者单位 | 1.Anhui Univ, Inst Phys Sci & Informat Technol, Hefei, Anhui, Peoples R China 2.Shandong Univ, Qilu Hosp, Cheeloo Coll Med, NHC Key Lab Otorhinolaryngol, Jinan, Shandong, Peoples R China 3.Shandong Univ, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Natl Hlth Commiss, Chinese Minist Educ,Qilu Hosp, Jinan, Peoples R China 4.Shandong Univ, Brain Res Inst, Qilu Hosp, Jinan, Shandong, Peoples R China 5.Shandong Univ, Dept Neurol, Qilu Hosp, Jinan, Shandong, Peoples R China 6.Univ Sci & Technol China, Hefei, Anhui, Peoples R China 7.Chinese Acad Sci, Hefei Inst Phys Sci, High Magnet Field Lab, Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei, Anhui, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Youjia,Yang, Xiaxin,Liu, Yongrui,et al. Vav2 is a novel APP-interacting protein that regulates APP protein level[J]. SCIENTIFIC REPORTS,2022,12. |
| APA | Zhang, Youjia.,Yang, Xiaxin.,Liu, Yongrui.,Ge, Liang.,Wang, Jiarong.,...&Wang, Junfeng.(2022).Vav2 is a novel APP-interacting protein that regulates APP protein level.SCIENTIFIC REPORTS,12. |
| MLA | Zhang, Youjia,et al."Vav2 is a novel APP-interacting protein that regulates APP protein level".SCIENTIFIC REPORTS 12(2022). |
入库方式： OAI收割
来源：合肥物质科学研究院
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