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PKC theta/beta and CYLD Are Antagonistic Partners in the NF kappa B and NFAT Transactivation Pathways in Primary Mouse CD3(+) T Lymphocytes

Thuille, Nikolaus ; Wachowicz, Katarzyna ; Hermann-Kleiter, Natascha ; Kaminski, Sandra ; Fresser, Friedrich ; Lutz-Nicoladoni, Christina ; Leitges, Michael ; Thome, Margot ; Massoumi, Ramin LU and Baier, Gottfried (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)
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organization
publishing date
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}},
}