磷酸蛋白质组学
生物
蛋白质组学
蛋白质组
细胞生物学
系统生物学
细胞培养中氨基酸的稳定同位素标记
蛋白质稳态
信号转导
磷酸化
计算生物学
定量蛋白质组学
生物发生
细胞信号
蛋白质磷酸化
生物信息学
生物化学
蛋白激酶A
基因
作者
Haiyan Tan,Kai Yang,Yuxin Li,Timothy I. Shaw,Yanyan Wang,Daniel Bastardo Blanco,Xusheng Wang,Ji-Hoon Cho,Hong Wang,Sherri L. Rankin,Clifford S. Guy,Junmin Peng,Hongbo Chi
出处
期刊:Immunity
[Elsevier]
日期:2017-03-01
卷期号:46 (3): 488-503
被引量:256
标识
DOI:10.1016/j.immuni.2017.02.010
摘要
The molecular circuits by which antigens activate quiescent T cells remain poorly understood. We combined temporal profiling of the whole proteome and phosphoproteome via multiplexed isobaric labeling proteomics technology, computational pipelines for integrating multi-omics datasets, and functional perturbation to systemically reconstruct regulatory networks underlying T cell activation. T cell receptors activated the T cell proteome and phosphoproteome with discrete kinetics, marked by early dynamics of phosphorylation and delayed ribosome biogenesis and mitochondrial activation. Systems biology analyses identified multiple functional modules, active kinases, transcription factors and connectivity between them, and mitochondrial pathways including mitoribosomes and complex IV. Genetic perturbation revealed physiological roles for mitochondrial enzyme COX10-mediated oxidative phosphorylation in T cell quiescence exit. Our multi-layer proteomics profiling, integrative network analysis, and functional studies define landscapes of the T cell proteome and phosphoproteome and reveal signaling and bioenergetics pathways that mediate lymphocyte exit from quiescence.
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