MAPK/ERK signaling in activated T cells inhibits CD95/Fas-mediated apoptosis downstream of DISC assembly

• Verfasst von: Holmström, Tim [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Titel: MAPK/ERK signaling in activated T cells inhibits CD95/Fas-mediated apoptosis downstream of DISC assembly
• Verf.angabe: Tim H. Holmström, Ingo Schmitz, Thomas S. Söderström, Minna Poukkula, Victoria L. Johnson, Sek C. Chow, Peter H. Krammer and John E. Eriksson
• E-Jahr: 2000
• Jahr: 16 October 2000
• Umfang: 11 S.
• Teil: volume:19
• Teil: year:2000
• Teil: number:20
• Teil: pages:5418-5428
• Teil: extent:11
• Fussnoten: Gesehen am 26.04.2021
• Titel Quelle: Enthalten in: European Molecular Biology OrganizationThe EMBO journal
• Ort Quelle: Heidelberg : EMBO Press, 1982
• Jahr Quelle: 2000
• Band/Heft Quelle: 19(2000), 20, Seite 5418-5428
• ISSN Quelle: 1460-2075
• DOI: doi:10.1093/emboj/19.20.5418
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: apoptosis
• Sach-SW: death receptor
• Sach-SW: MAP kinase
• Sach-SW: T cell activation
• Sach-SW: T cell receptor
• K10plus-PPN: 1755925816

Abstract

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.