The integration of multiple signalling pathways that co-ordinate T cell metabolism and transcriptional reprogramming is required to drive T cell differentiation and proliferation. One key T cell signalling module is mediated by extracellular signal-regulated kinases (ERKs) which are activated in response to antigen receptor engagement. The activity of ERKs is often used to report antigen receptor occupancy but the full details of how ERKs control T cell activation is not understood. Accordingly, we have used mass spectrometry to explore how ERK signalling pathways control antigen receptor driven proteome restructuring in CD8+ T cells to gain insights about the biological processes controlled by ERKs in primary lymphocytes. Quantitative analysis of >8000 proteins identified 900 ERK regulated proteins in activated CD8+ T cells. The data identify both positive and negative regulatory roles for ERKs during T cell activation and reveal that ERK signalling primarily controls the repertoire of transcription factors, cytokines and cytokine receptors expressed by activated T cells. It was striking that a large proportion of the proteome restructuring that is driven by triggering of the T cell antigen receptor is not dependent on ERK activation. However, the selective targets of the ERK signalling module include the critical effector molecules and the cytokines that allow T cell communication with other immune cells to mediate adaptive immune responses.

中文翻译：

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CD8+ T 细胞分化的细胞外信号调节激酶 (ERK) 通路控制

协调 T 细胞代谢和转录重编程的多种信号通路的整合是驱动 T 细胞分化和增殖所必需的。一个关键的 T 细胞信号传导模块由细胞外信号调节激酶 (ERK) 介导，这些激酶响应抗原受体的结合而被激活。ERKs 的活性通常用于报告抗原受体的占有率，但尚不清楚 ERKs 如何控制 T 细胞活化的全部细节。因此，我们使用质谱来探索 ERK 信号通路如何控制 CD8+ T 细胞中抗原受体驱动的蛋白质组重组，以深入了解原代淋巴细胞中由 ERK 控制的生物过程。> 8000 种蛋白质的定量分析在活化的 CD8+ T 细胞中鉴定了 900 种 ERK 调节的蛋白质。数据确定了 ERK 在 T 细胞活化过程中的积极和消极调节作用，并表明 ERK 信号传导主要控制活化 T 细胞表达的转录因子、细胞因子和细胞因子受体的库。令人惊讶的是，大部分由 T 细胞抗原受体触发驱动的蛋白质组重组不依赖于 ERK 激活。然而，ERK 信号模块的选择性靶标包括关键效应分子和允许 T 细胞与其他免疫细胞通讯以介导适应性免疫反应的细胞因子。活化的 T 细胞表达的细胞因子和细胞因子受体。令人惊讶的是，大部分由 T 细胞抗原受体触发驱动的蛋白质组重组不依赖于 ERK 激活。然而，ERK 信号模块的选择性靶标包括关键效应分子和允许 T 细胞与其他免疫细胞通讯以介导适应性免疫反应的细胞因子。活化的 T 细胞表达的细胞因子和细胞因子受体。令人惊讶的是，大部分由 T 细胞抗原受体触发驱动的蛋白质组重组不依赖于 ERK 激活。然而，ERK 信号模块的选择性靶标包括关键效应分子和允许 T 细胞与其他免疫细胞通讯以介导适应性免疫反应的细胞因子。