MAPK/ERK signaling in activated T cells inhibits CD95/Fas-mediated apoptosis downstream of DISC assembly
When T cells are activated, the expression of the CD95 ligand is elevated, with the purpose of inducing apoptosis in target cells and to later eliminate the activated T cells. We have shown previously that mitogen-activated protein kinase (MAPK or ERK) signaling suppresses CD95-mediated apoptosis in...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
16 October 2000
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| In: |
The EMBO journal
Year: 2000, Volume: 19, Issue: 20, Pages: 5418-5428 |
| ISSN: | 1460-2075 |
| DOI: | 10.1093/emboj/19.20.5418 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/emboj/19.20.5418 Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.1093/emboj/19.20.5418 
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| Author Notes: | Tim H. Holmström, Ingo Schmitz, Thomas S. Söderström, Minna Poukkula, Victoria L. Johnson, Sek C. Chow, Peter H. Krammer and John E. Eriksson |
| Summary: | When T cells are activated, the expression of the CD95 ligand is elevated, with the purpose of inducing apoptosis in target cells and to later eliminate the activated T cells. We have shown previously that mitogen-activated protein kinase (MAPK or ERK) signaling suppresses CD95-mediated apoptosis in different cellular systems. In this study we examined whether MAPK signaling controls the persistence and CD95-mediated termination of an immune response in activated T cells. Our results show that activation of Jurkat T cells through the T cell receptor immediately suppresses CD95-mediated apoptosis, and that this suppression is mediated by MAPK activation. During the phase of elevated MAPK activity, the activation of caspase-8 and Bid is inhibited, whereas the assembly of a functional death-inducing signaling complex (DISC) is not affected. These results explain the resistance to CD95 responses observed during the early phase of T cell activation and suggest that MAPK-activation deflects DISC signaling from activating caspase-8 and Bid. The physiological relevance of the results was confirmed in activated primary peripheral T cells, in which inhibition of MAPK signaling markedly sensitized the cells to CD95-mediated apoptosis. |
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| Item Description: | Gesehen am 26.04.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1460-2075 |
| DOI: | 10.1093/emboj/19.20.5418 |