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 and phosphoproteome 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.