PKCθ/β and CYLD are antagonistic partners in the NFκB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes.
In T cells PKCθ mediates the activation of critical signals downstream of TCR/CD28 stimulation. We investigated the molecular mechanisms by which PKCθ regulates NFκB transactivation by examining PKCθ/β single and double knockout mice and observed a redundant involvement of PKCθ and PKCβ in this sign...
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2013
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oai:doaj.org-article:b1dfabdaa5b8404d82f6bee9d2a783952021-11-18T08:01:25ZPKCθ/β and CYLD are antagonistic partners in the NFκB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes.1932-620310.1371/journal.pone.0053709https://doaj.org/article/b1dfabdaa5b8404d82f6bee9d2a783952013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23335970/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203In T cells PKCθ mediates the activation of critical signals downstream of TCR/CD28 stimulation. We investigated the molecular mechanisms by which PKCθ regulates NFκB transactivation by examining PKCθ/β single and double knockout mice and observed a redundant involvement of PKCθ and PKCβ in this signaling pathway. Mechanistically, we define a PKCθ-CYLD protein complex and an interaction between the positive PKCθ/β and the negative CYLD signaling pathways that both converge at the level of TAK1/IKK/I-κBα/NFκB 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 PKCθ/CYLD complex appears to regulate the short-term spatial distribution of CYLD, subsequently affecting NFκB and NFAT repressional activity of CYLD prior to its MALT1-dependent inactivation. Taken together, our study establishes CYLD as a new and critical PKCθ interactor in T cells and reveals that antagonistic PKCθ/β-CYLD crosstalk is crucial for the adjustment of immune thresholds in primary mouse CD3(+) T cells.Nikolaus ThuilleKatarzyna WachowiczNatascha Hermann-KleiterSandra KaminskiFriedrich FresserChristina Lutz-NicoladoniMichael LeitgesMargot ThomeRamin MassoumiGottfried BaierPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53709 (2013) |
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DOAJ |
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Medicine R Science Q |
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Medicine R Science Q Nikolaus Thuille Katarzyna Wachowicz Natascha Hermann-Kleiter Sandra Kaminski Friedrich Fresser Christina Lutz-Nicoladoni Michael Leitges Margot Thome Ramin Massoumi Gottfried Baier PKCθ/β and CYLD are antagonistic partners in the NFκB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes. |
| description |
In T cells PKCθ mediates the activation of critical signals downstream of TCR/CD28 stimulation. We investigated the molecular mechanisms by which PKCθ regulates NFκB transactivation by examining PKCθ/β single and double knockout mice and observed a redundant involvement of PKCθ and PKCβ in this signaling pathway. Mechanistically, we define a PKCθ-CYLD protein complex and an interaction between the positive PKCθ/β and the negative CYLD signaling pathways that both converge at the level of TAK1/IKK/I-κBα/NFκB 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 PKCθ/CYLD complex appears to regulate the short-term spatial distribution of CYLD, subsequently affecting NFκB and NFAT repressional activity of CYLD prior to its MALT1-dependent inactivation. Taken together, our study establishes CYLD as a new and critical PKCθ interactor in T cells and reveals that antagonistic PKCθ/β-CYLD crosstalk is crucial for the adjustment of immune thresholds in primary mouse CD3(+) T cells. |
| format |
article |
| author |
Nikolaus Thuille Katarzyna Wachowicz Natascha Hermann-Kleiter Sandra Kaminski Friedrich Fresser Christina Lutz-Nicoladoni Michael Leitges Margot Thome Ramin Massoumi Gottfried Baier |
| author_facet |
Nikolaus Thuille Katarzyna Wachowicz Natascha Hermann-Kleiter Sandra Kaminski Friedrich Fresser Christina Lutz-Nicoladoni Michael Leitges Margot Thome Ramin Massoumi Gottfried Baier |
| author_sort |
Nikolaus Thuille |
| title |
PKCθ/β and CYLD are antagonistic partners in the NFκB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes. |
| title_short |
PKCθ/β and CYLD are antagonistic partners in the NFκB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes. |
| title_full |
PKCθ/β and CYLD are antagonistic partners in the NFκB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes. |
| title_fullStr |
PKCθ/β and CYLD are antagonistic partners in the NFκB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes. |
| title_full_unstemmed |
PKCθ/β and CYLD are antagonistic partners in the NFκB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes. |
| title_sort |
pkcθ/β and cyld are antagonistic partners in the nfκb and nfat transactivation pathways in primary mouse cd3+ t lymphocytes. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/b1dfabdaa5b8404d82f6bee9d2a78395 |
| work_keys_str_mv |
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