PKC theta/beta and CYLD Are Antagonistic Partners in the NF kappa B and NFAT Transactivation Pathways in Primary Mouse CD3(+) T Lymphocytes
(2013) In PLoS ONE 8(1).- Abstract
- In T cells PKC theta mediates the activation of critical signals downstream of TCR/CD28 stimulation. We investigated the molecular mechanisms by which PKC theta regulates NF kappa B transactivation by examining PKC theta/beta single and double knockout mice and observed a redundant involvement of PKCh and PKC beta in this signaling pathway. Mechanistically, we define a PKC theta-CYLD protein complex and an interaction between the positive PKC theta/beta and the negative CYLD signaling pathways that both converge at the level of TAK1/IKK/I-kB alpha/NF kappa B and NFAT transactivation. In Jurkat leukemic T cells, CYLD is endoproteolytically processed in the initial minutes of stimulation by the paracaspase MALT1 in a PKC-dependent fashion,... (More)
- In T cells PKC theta mediates the activation of critical signals downstream of TCR/CD28 stimulation. We investigated the molecular mechanisms by which PKC theta regulates NF kappa B transactivation by examining PKC theta/beta single and double knockout mice and observed a redundant involvement of PKCh and PKC beta in this signaling pathway. Mechanistically, we define a PKC theta-CYLD protein complex and an interaction between the positive PKC theta/beta and the negative CYLD signaling pathways that both converge at the level of TAK1/IKK/I-kB alpha/NF kappa B and NFAT transactivation. In Jurkat leukemic T cells, CYLD is endoproteolytically processed in the initial minutes of stimulation by the paracaspase MALT1 in a PKC-dependent fashion, which is required for robust IL-2 transcription. However, in primary T cells, CYLD processing occurs with different kinetics and an altered dependence on PKC. The formation of a direct PKC theta/CYLD complex appears to regulate the short-term spatial distribution of CYLD, subsequently affecting NF kappa B and NFAT repressional activity of CYLD prior to its MALT1dependent inactivation. Taken together, our study establishes CYLD as a new and critical PKC theta interactor in T cells and reveals that antagonistic PKC theta/beta-CYLD crosstalk is crucial for the adjustment of immune thresholds in primary mouse CD3(+) T cells. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3580961
- author
- Thuille, Nikolaus ; Wachowicz, Katarzyna ; Hermann-Kleiter, Natascha ; Kaminski, Sandra ; Fresser, Friedrich ; Lutz-Nicoladoni, Christina ; Leitges, Michael ; Thome, Margot ; Massoumi, Ramin LU and Baier, Gottfried
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 8
- issue
- 1
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000314707700026
- scopus:84872395016
- pmid:23335970
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0053709
- language
- English
- LU publication?
- yes
- id
- 53d96179-4ab5-4d7d-a367-9c178dc6276d (old id 3580961)
- date added to LUP
- 2016-04-01 14:45:47
- date last changed
- 2022-03-22 01:51:37
@article{53d96179-4ab5-4d7d-a367-9c178dc6276d, abstract = {{In T cells PKC theta mediates the activation of critical signals downstream of TCR/CD28 stimulation. We investigated the molecular mechanisms by which PKC theta regulates NF kappa B transactivation by examining PKC theta/beta single and double knockout mice and observed a redundant involvement of PKCh and PKC beta in this signaling pathway. Mechanistically, we define a PKC theta-CYLD protein complex and an interaction between the positive PKC theta/beta and the negative CYLD signaling pathways that both converge at the level of TAK1/IKK/I-kB alpha/NF kappa B and NFAT transactivation. In Jurkat leukemic T cells, CYLD is endoproteolytically processed in the initial minutes of stimulation by the paracaspase MALT1 in a PKC-dependent fashion, which is required for robust IL-2 transcription. However, in primary T cells, CYLD processing occurs with different kinetics and an altered dependence on PKC. The formation of a direct PKC theta/CYLD complex appears to regulate the short-term spatial distribution of CYLD, subsequently affecting NF kappa B and NFAT repressional activity of CYLD prior to its MALT1dependent inactivation. Taken together, our study establishes CYLD as a new and critical PKC theta interactor in T cells and reveals that antagonistic PKC theta/beta-CYLD crosstalk is crucial for the adjustment of immune thresholds in primary mouse CD3(+) T cells.}}, author = {{Thuille, Nikolaus and Wachowicz, Katarzyna and Hermann-Kleiter, Natascha and Kaminski, Sandra and Fresser, Friedrich and Lutz-Nicoladoni, Christina and Leitges, Michael and Thome, Margot and Massoumi, Ramin and Baier, Gottfried}}, issn = {{1932-6203}}, language = {{eng}}, number = {{1}}, publisher = {{Public Library of Science (PLoS)}}, series = {{PLoS ONE}}, title = {{PKC theta/beta and CYLD Are Antagonistic Partners in the NF kappa B and NFAT Transactivation Pathways in Primary Mouse CD3(+) T Lymphocytes}}, url = {{https://lup.lub.lu.se/search/files/4150449/3736681.pdf}}, doi = {{10.1371/journal.pone.0053709}}, volume = {{8}}, year = {{2013}}, }