Ultra-deep tyrosine phosphoproteomics enabled by a phosphotyrosine superbinder

doi:10.1038/NCHEMBIO.2178

	Ultra-deep tyrosine phosphoproteomics enabled by a phosphotyrosine superbinder
	Liu, Xuguang 2; Bian, Yangyang 1,6; Li, Lei 2,3; Dong, Mingming 1,6; Kaneko, Tomonori 2; Cheng, Kai 6; Liu, Huadong 2; Voss, Courtney 2; Cao, Xuan 2; Wang, Yan
刊名	NATURE CHEMICAL BIOLOGY
	2016-11-01
卷号	12 期号:11 页码:959-+
ISSN号	1552-4450
DOI	10.1038/NCHEMBIO.2178
文献子类	Article
英文摘要	We present a new strategy for systematic identification of phosphotyrosine (pTyr) by affinity purification mass spectrometry (AP-MS) using a Src homology 2 (SH2)-domain-derived pTyr superbinder as the affinity reagent. The superbinder allows for markedly deeper coverage of the Tyr phosphoproteome than anti-pTyr antibodies when an optimal amount is used. We identified similar to 20,000 distinct phosphotyrosyl peptides and >10,000 pTyr sites, of which 36% were 'novel', from nine human cell lines using the superbinder approach. Tyrosine kinases, SH2 domains and phosphotyrosine phosphatases were preferably phosphorylated, suggesting that the toolkit of kinase signaling is subject to intensive regulation by phosphorylation. Cell-type-specific global kinase activation patterns inferred from label-free quantitation of Tyr phosphorylation guided the design of experiments to inhibit cancer cell proliferation by blocking the highly activated tyrosine kinases. Therefore, the superbinder is a highly efficient and cost-effective alternative to conventional antibodies for systematic and quantitative characterization of the tyrosine phosphoproteome under normal or pathological conditions.
WOS关键词	ION AFFINITY-CHROMATOGRAPHY ; BREAST-CANCER CELLS ; FACTOR-I RECEPTOR ; POSTTRANSLATIONAL MODIFICATIONS ; PHOSPHORYLATION DYNAMICS ; SIGNALING NETWORKS ; MASS-SPECTROMETRY ; ACTIVATION LOOP ; HUMAN PROTEOME ; LUNG-CANCER
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000386798800018
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/169894]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Ye, Mingliang; Li, Shawn S-C; Zou, Hanfa
作者单位	1.Univ Chinese Acad Sci, Beijing, Peoples R China 2.Western Univ, Dept Biochem, Schulich Sch Med & Dent, London, ON, Canada 3.Qingdao Univ, Sch Basic Med Sci, Qingdao, Peoples R China 4.Western Univ, Schulich Sch Med & Dent, Childrens Hlth Res Inst, London, ON, Canada 5.Western Univ, Schulich Sch Med & Dent, Dept Oncol, London, ON, Canada 6.Chinese Acad Sci, Dalian Inst Chem Phys, Natl Chromatog R&D Ctr, Key Lab Separat Sci Analyt Chem, Dalian, Peoples R China
推荐引用方式 GB/T 7714	Liu, Xuguang,Bian, Yangyang,Li, Lei,et al. Ultra-deep tyrosine phosphoproteomics enabled by a phosphotyrosine superbinder[J]. NATURE CHEMICAL BIOLOGY,2016,12(11):959-+.
APA	Liu, Xuguang.,Bian, Yangyang.,Li, Lei.,Dong, Mingming.,Kaneko, Tomonori.,...&Zou, Hanfa.(2016).Ultra-deep tyrosine phosphoproteomics enabled by a phosphotyrosine superbinder.NATURE CHEMICAL BIOLOGY,12(11),959-+.
MLA	Liu, Xuguang,et al."Ultra-deep tyrosine phosphoproteomics enabled by a phosphotyrosine superbinder".NATURE CHEMICAL BIOLOGY 12.11(2016):959-+.