RT Journal Article SR Electronic T1 Extracellular signal-regulated kinase (ERK) pathway control of CD8+ T cell differentiation JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.08.18.255711 DO 10.1101/2020.08.18.255711 A1 Marcos P. Damasio A1 Julia M. Marchingo A1 Laura Spinelli A1 Doreen A. Cantrell A1 Andrew J.M. Howden YR 2020 UL http://biorxiv.org/content/early/2020/08/18/2020.08.18.255711.abstract AB 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 only 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. The ERKs thus drive the transcriptional reprogramming of activated T cells and the ability of T cells to communicate with external immune cues.Competing Interest StatementThe authors have declared no competing interest.