Integrative proteomics and phosphoproteomics profiling and systems biology analysis reveal dynamic signaling networks and mTORC1-dependent mitochondrial function in T cell activation

The underlying mechanisms by which naïve T cells exit from quiescence after antigen stimulation remain elusive. Using multiplex isobaric labeling proteomics technology, we report unbiased, temporal profiling of whole proteome (>8,000 proteins) and phosphoproteome (>13,000 phosphopeptides) during the activation in the wild type and Rptor-/- T cells. TCR stimulation results in dynamic reprogramming of the proteome and phosphoproteome, with predominant upregulation of molecular machineries in protein translation and mitochondrial activation. Loss of mTORC1 disrupts TCR-induced mitochondrial functions including mitoribosome biogenesis, one-carbon metabolism and oxidative phosphorylation.

抗原刺激后初始T细胞（naïve T cells）脱离静息状态的潜在机制仍未明确。本研究采用多重同重同位素标记蛋白质组学技术，对野生型与Rptor-/- T细胞活化过程中的全蛋白质组（proteome，>8000种蛋白质）与磷酸化蛋白质组（phosphoproteome，>13000条磷酸肽）进行了无偏倚的时间剖面分析。T细胞受体（T cell receptor, TCR）刺激可引发蛋白质组与磷酸化蛋白质组的动态重编程，其中参与蛋白质翻译与线粒体激活的分子机器显著上调。哺乳动物雷帕霉素靶蛋白复合物1（mTORC1）缺失会破坏TCR诱导的线粒体功能，包括线粒体核糖体生物发生、一碳代谢与氧化磷酸化过程。