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

Marcos P. Damasio, Julia M. Marchingo, Laura Spinelli, Jens L. Hukelmann, Doreen A. Cantrell (Lead / Corresponding author), Andrew J. M. Howden (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

4 Downloads (Pure)

Abstract

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.
Original languageEnglish
Pages (from-to)79-98
Number of pages20
JournalBiochemical Journal
Volume478
Issue number1
Early online date11 Dec 2020
DOIs
Publication statusPublished - 13 Jan 2021

Keywords

  • extracellular signal-regulated kinases
  • proteomics
  • T-cells

Fingerprint Dive into the research topics of 'Extracellular signal-regulated kinase (ERK) pathway control of CD8<sup>+</sup> T cell differentiation'. Together they form a unique fingerprint.

Cite this