Extracellular signal-regulated kinase (ERK) pathway control of CD8+ T cell differentiation
| Autor: | Julia M. Marchingo, Doreen A. Cantrell, Andrew J. M. Howden, Laura Spinelli, Marcos Damasio, Jens L. Hukelmann |
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| Rok vydání: | 2021 |
| Předmět: |
DNA Replication
Male Proteomics MAPK/ERK pathway Proteome Cell Survival MAP Kinase Signaling System medicine.medical_treatment T cell Apoptosis Mice Transgenic CD8-Positive T-Lymphocytes Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Tandem Mass Spectrometry medicine Animals Cytotoxic T cell Extracellular Signal-Regulated MAP Kinases Receptor Protein Kinase Inhibitors Molecular Biology Cell Proliferation 030304 developmental biology 0303 health sciences Chemistry Kinase Lymphopoiesis Cell Cycle Cell Biology Cell biology Gene Ontology Cytokine medicine.anatomical_structure T cell differentiation Benzamides Cytokines Female 030217 neurology & neurosurgery CD8 Chromatography Liquid Transcription Factors |
| Zdroj: | Biochemical Journal. 478:79-98 |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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