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
| Autor: | A, Villunger, N, Ghaffari-Tabrizi, I, Tinhofer, N, Krumböck, B, Bauer, T, Schneider, S, Kasibhatla, R, Greil, G, Baier-Bitterlich, F, Uberall, D R, Green, G, Baier |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Transcriptional Activation
Fas Ligand Protein Transcription Genetic MAP Kinase Signaling System Antigens Polyomavirus Transforming Gene Expression MAP Kinase Kinase Kinase 1 Apoptosis Protein Serine-Threonine Kinases Ligands Jurkat Cells Viral Proteins Humans Promoter Regions Genetic Protein Kinase C Serpins Membrane Glycoproteins Calcineurin Ionomycin NF-kappa B MAP Kinase Kinase Kinases Isoenzymes Transcription Factor AP-1 Protein Kinase C-theta Tetradecanoylphorbol Acetate Mitogens Signal Transduction |
| Zdroj: | European journal of immunology. 29(11) |
| ISSN: | 0014-2980 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text