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 after TCR stimulation. 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 after TCR engagement. Among proteins whose phosphorylation was regulated by TCR stimulation, we demonstrated, using a fast‐track gene inactivation approach in primary lymphocytes, that the ITSN 2 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: https://bmm-lab.github.io/LymphoAtlas.

中文翻译：

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LymphoAtlas：原代 T 细胞中 TCR 信号传导的动态且整合的磷酸蛋白质组学资源揭示了 ITSN2 作为效应器功能的调节器。

T 细胞受体 (TCR) 连接介导的蛋白质磷酸化调节 T 细胞的激活、细胞反应和命运。在这里，我们使用时间分辨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态。对数据的生物信息分析揭示了 T 细胞激活背后的生物过程的连贯编排。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 参与后几秒钟内被调动起来。在磷酸化受 TCR 刺激调节的蛋白质中，我们使用原代淋巴细胞中的快速基因失活方法证明，ITSN 2 接头蛋白调节 T 细胞效应器功能。该资源称为 LymphoAtlas，代表了一个集成管道，可进一步破译编码 T 细胞激活的信号网络的组织。LymphoAtlas 可供社区访问：https://bmm-lab.github.io/LymphoAtlas。