LymphoAtlas: a dynamic and integrated phosphoproteomic resource ofTCRsignaling in primary T cells revealsITSN2 as a regulator of effector functions
LymphoAtlas: a dynamic and integrated phosphoproteomic resource ofTCRsignaling in primary T cells revealsITSN2 as a regulator of effector functions
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DOI：
10.15252/msb.20209524
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发表时间：
2020-07-01
影响因子：
9.9
通讯作者：
Roncagalli, Romain
中科院分区：
文献类型：
--
作者：
Locard-Paulet, Marie;Voisinne, Guillaume;Roncagalli, Romain
T细胞受体（TCR）连接介导的蛋白磷酸化调节T细胞的活化、细胞应答和命运。在这里，我们使用时间分辨的高分辨率磷酸化蛋白质组学来识别，量化和表征TCR刺激后前10分钟内原代T细胞中数千个磷酸化位点的磷酸化动力学。对数据的生物信息学分析揭示了T细胞活化背后的生物过程的一致协调。特别是，与细胞骨架重塑，转录，翻译和代谢过程相关的功能模块在TCR参与后几秒钟内被动员。在其磷酸化受TCR刺激调节的蛋白质中，我们在初级淋巴细胞中使用快速基因失活方法证明了ITSN 2衔接蛋白调节T细胞效应功能。这个资源，称为AphphoAtlas，代表了一个集成的管道，以进一步破译编码T细胞激活的信号网络的组织。社区可通过以下网址访问该网站：
T-cell receptor (TCR) ligation-mediated protein phosphorylation regulates the activation, cellular responses, and fates of T cells. Here, we used time-resolved high-resolution phosphoproteomics to identify, quantify, and characterize the phosphorylation dynamics of thousands of phosphorylation sites in primary T cells during the first 10 min afterTCRstimulation. Bioinformatic analysis of the data revealed a coherent orchestration of biological processes underlying T-cell activation. In particular, functional modules associated with cytoskeletal remodeling, transcription, translation, and metabolic processes were mobilized within seconds afterTCRengagement. Among proteins whose phosphorylation was regulated byTCRstimulation, we demonstrated, using a fast-track gene inactivation approach in primary lymphocytes, that theITSN2 adaptor protein regulated T-cell effector functions. This resource, called LymphoAtlas, represents an integrated pipeline to further decipher the organization of the signaling network encoding T-cell activation. LymphoAtlas is accessible to the community at: .