| First Author | Ruefli-Brasse AA | Year | 2004 |
| Journal | J Biol Chem | Volume | 279 |
| Issue | 2 | Pages | 1570-4 |
| PubMed ID | 14638696 | Mgi Jnum | J:87716 |
| Mgi Id | MGI:3027457 | Doi | 10.1074/jbc.C300460200 |
| Citation | Ruefli-Brasse AA, et al. (2004) Rip2 participates in Bcl10 signaling and T-cell receptor-mediated NF-kappaB activation. J Biol Chem 279(2):1570-4 |
| abstractText | Engagement of the T-cell receptor (TCR) initiates a signaling cascade that ultimately results in activation of the transcription factor NF-kappaB, which regulates many T-cell functions including proliferation, differentiation and cytokine production. Herein we demonstrate that Rip2, a caspase recruitment domain (CARD)-containing serine/threonine kinase, plays an important role in this cascade and is required for optimal TCR signaling and NF-kappaB activation. Following TCR engagement, Rip2 associated with Bcl10, a CARD-containing signaling component of the TCR-induced NF-kappaB pathway, and induced its phosphorylation. Rip2-deficient mice were defective in TCR-induced NF-kappaB activation, interleukin-2 production, and proliferation in vitro and exhibited defective T-cell-dependent responses in vivo. The defect in Rip2-/- T-cells correlated with a lack of TCR-induced Bcl10 phosphorylation. Furthermore, deficiency in Bcl10-dependent NF-kappaB activation could be rescued in Rip2-/- embryonic fibroblasts by exogenous wild-type Rip2 but not a kinase-dead mutant. Together these data define an important role for Rip2 in TCR-induced NF-kappaB activation and T-cell function and highlight the significance of post-translational modification of Bcl10 by Rip2 in T-cell signaling. |
