Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Villunger, A; Ghaffari-Tabrizi, N; Tinhofer, I; Krumböck, N; Bauer, B; Schneider, T; Kasibhatla, S; Greil, R; Baier-Bitterlich, G; Uberall, F; Green, DR; Baier, G.
Synergistic action of protein kinase C theta and calcineurin is sufficient for Fas ligand expression and induction of a crmA-sensitive apoptosis pathway in Jurkat T cells.
Eur J Immunol. 1999; 29(11):3549-3561
Doi: 10.1002/(SICI)1521-4141(199911)29:11<3549::AID-IMMU3549>3.0.CO;2-Q
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PubMed
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- Co-Autor*innen der Med Uni Graz
- Ghaffari Tabrizi-Wizsy Nassim
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- Abstract:
- Deletion of activated peripheral T cell clones by apoptosis requires the regulated expression of Fas ligand (FasL) and sensitization of these cells to CD95-mediated signaling. To investigate the signaling pathways responsible for FasL expression in T cells, we tested-besides subfamily-selective protein kinase C (PKC) inhibitors - the effect of constitutively active mutants of representatives of all PKC subfamilies, i.e. PKCalpha,epsilon,theta,iota, on FasL luciferase promoter reporter constructs. In synergy with a constitutively active form of protein phosphatase 2B calcineurin (CaN), only PKCtheta, but not PKCalpha,epsilon,iota, preferentially induced FasL promoter reporter activity and, consequently, FasL protein expression in Jurkat T cells. Activation of an inducible PKCtheta AE-estrogen receptor fusion mutant led to a CaN-dependent and rapid FasL reporter activity detected as early as 4 h after addition of 4-hydroxytamoxifen, incidating a direct effect of PKCtheta action on FasL expression. Consistently, in Jurkat T cells, expression of PKCtheta AE / CaN significantly enhanced FasL protein expression and apoptosis in a CD95-dependent manner since cell death was not observed in T cells co-expressing the caspase-8 inhibitor crmA. Taken together, our results support the notion that PKCtheta and CaN are sufficient to regulate apoptosis through FasL expression.
- Find related publications in this database (using NLM MeSH Indexing)
- Antigens, Polyomavirus Transforming - genetics
- Apoptosis - genetics
- Calcineurin - genetics
- Fas Ligand Protein - genetics
- Gene Expression - genetics
- Humans - genetics
- Ionomycin - pharmacology
- Isoenzymes - genetics
- Jurkat Cells - genetics
- Ligands - genetics
- MAP Kinase Kinase Kinase 1 - genetics
- MAP Kinase Kinase Kinases - metabolism
- MAP Kinase Signaling System - metabolism
- Membrane Glycoproteins - biosynthesis
- Mitogens - pharmacology
- NF-kappa B - metabolism
- Promoter Regions, Genetic - metabolism
- Protein Kinase C - genetics
- Protein-Serine-Threonine Kinases - genetics
- Serpins - metabolism
- Signal Transduction - metabolism
- Tetradecanoylphorbol Acetate - pharmacology
- Transcription Factor AP-1 - metabolism
- Transcription, Genetic - metabolism
- Transcriptional Activation - metabolism
- Viral Proteins - metabolism
- Find related publications in this database (Keywords)
- Fas ligand
- protein kinase C theta
- calcineurin
- Rac
- MEKK
- AP-1