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Extracellular signal-regulated kinase (ERK) pathway control of CD8+ T cell differentiation

Marcos P. Damasio, View ORCID ProfileJulia M. Marchingo, Laura Spinelli, View ORCID ProfileDoreen A. Cantrell, View ORCID ProfileAndrew J.M. Howden
doi: https://doi.org/10.1101/2020.08.18.255711
Marcos P. Damasio
1Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, DD1 5EH, UK
2Massachusetts General Hospital, 55 Fruit street, Boston, Massachusetts, 02114, USA
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Julia M. Marchingo
1Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, DD1 5EH, UK
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Laura Spinelli
1Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, DD1 5EH, UK
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Doreen A. Cantrell
1Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, DD1 5EH, UK
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  • For correspondence: d.a.cantrell@dundee.ac.uk a.howden@dundee.ac.uk
Andrew J.M. Howden
1Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, DD1 5EH, UK
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  • For correspondence: d.a.cantrell@dundee.ac.uk a.howden@dundee.ac.uk
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Summary

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 Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted August 18, 2020.
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Extracellular signal-regulated kinase (ERK) pathway control of CD8+ T cell differentiation
Marcos P. Damasio, Julia M. Marchingo, Laura Spinelli, Doreen A. Cantrell, Andrew J.M. Howden
bioRxiv 2020.08.18.255711; doi: https://doi.org/10.1101/2020.08.18.255711
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Extracellular signal-regulated kinase (ERK) pathway control of CD8+ T cell differentiation
Marcos P. Damasio, Julia M. Marchingo, Laura Spinelli, Doreen A. Cantrell, Andrew J.M. Howden
bioRxiv 2020.08.18.255711; doi: https://doi.org/10.1101/2020.08.18.255711

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