Vav2 is a novel APP-interacting protein that regulates APP protein level

doi:10.1038/s41598-022-16883-z

HFCAS OpenIR

	Vav2 is a novel APP-interacting protein that regulates APP protein level
	Zhang, Youjia 1,2; Yang, Xiaxin 3,4; Liu, Yongrui 2; Ge, Liang 1; Wang, Jiarong1 ; Sun, Xiulian 4,5,6; Wu, Bo1 ; Wang, Junfeng 1,2,7
	2022-07-26
发表期刊	SCIENTIFIC REPORTS
ISSN	2045-2322
通讯作者	Sun, Xiulian(xiulians@gmail.com) ; Wu, Bo(wubo@hmfl.ac.cn) ; Wang, Junfeng(junfeng@hmfl.ac.cn)
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.
DOI	10.1038/s41598-022-16883-z
关键词[WOS]	AMYLOID PRECURSOR PROTEIN ; NUCLEOTIDE EXCHANGE FACTOR ; A-BETA-PP ; ALZHEIMERS-DISEASE ; STRUCTURAL BASIS ; FAMILY ; PHOSPHORYLATION ; BINDING ; FE65 ; IDENTIFICATION
收录类别	SCI
语种	英语
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
项目资助者	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
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000835004100047
出版者	NATURE PORTFOLIO
引用统计
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/132190
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.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 2.Univ Sci & Technol China, Hefei, Anhui, Peoples R China 3.Shandong Univ, Dept Neurol, Qilu Hosp, Jinan, Shandong, Peoples R China 4.Shandong Univ, Brain Res Inst, Qilu Hosp, Jinan, Shandong, Peoples R China 5.Shandong Univ, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Natl Hlth Commiss, Chinese Minist Educ,Qilu Hosp, Jinan, Peoples R China 6.Shandong Univ, Qilu Hosp, Cheeloo Coll Med, NHC Key Lab Otorhinolaryngol, Jinan, Shandong, Peoples R China 7.Anhui Univ, Inst Phys Sci & Informat Technol, 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).