| First Author | Thuille N | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 1 | Pages | e53709 |
| PubMed ID | 23335970 | Mgi Jnum | J:195859 |
| Mgi Id | MGI:5486075 | Doi | 10.1371/journal.pone.0053709 |
| Citation | Thuille N, et al. (2013) PKCtheta/beta and CYLD are antagonistic partners in the NFkappaB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes. PLoS One 8(1):e53709 |
| abstractText | In T cells PKCtheta mediates the activation of critical signals downstream of TCR/CD28 stimulation. We investigated the molecular mechanisms by which PKCtheta regulates NFkappaB transactivation by examining PKCtheta/beta single and double knockout mice and observed a redundant involvement of PKCtheta and PKCbeta in this signaling pathway. Mechanistically, we define a PKCtheta-CYLD protein complex and an interaction between the positive PKCtheta/beta and the negative CYLD signaling pathways that both converge at the level of TAK1/IKK/I-kappaBalpha/NFkappaB 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 PKCtheta/CYLD complex appears to regulate the short-term spatial distribution of CYLD, subsequently affecting NFkappaB and NFAT repressional activity of CYLD prior to its MALT1-dependent inactivation. Taken together, our study establishes CYLD as a new and critical PKCtheta interactor in T cells and reveals that antagonistic PKCtheta/beta-CYLD crosstalk is crucial for the adjustment of immune thresholds in primary mouse CD3(+) T cells. |
