| First Author | So T | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 7 | Pages | 2903-8 |
| PubMed ID | 21282629 | Mgi Jnum | J:169068 |
| Mgi Id | MGI:4939821 | Doi | 10.1073/pnas.1008765108 |
| Citation | So T, et al. (2011) Antigen-independent signalosome of CARMA1, PKC{theta}, and TNF receptor-associated factor 2 (TRAF2) determines NF-{kappa}B signaling in T cells. Proc Natl Acad Sci U S A 108(7):2903-8 |
| abstractText | NF-kappaB activation is essential for T-cell responses, and costimulatory molecules in the TNF receptor (TNFR) superfamily are viewed as a major source of this signal. Although the TNFR family recruits TNFR-associated factor (TRAF) molecules leading to IKKalpha/beta/gamma activation, it is not clear whether simple binding of TRAFs explains why they are such strong activators of NF-kappaB and so important for T-cell immunity. We now show that one TNFR family member, OX40 (CD134), after ligation by OX40L, assembles a unique complex that not only contains TRAF2, RIP, and IKKalpha/beta/gamma but also CARMA1, MALT1, BCL10, and PKC, molecules previously shown to regulate NF-kappaB activation through the T-cell receptor (TCR). The OX40 signalosome is formed in membrane microdomains irrespective of TCR engagement, and strongly promotes NF-kappaB activation only if CARMA1 and PKC are recruited. This NF-kappaB signal allows effector/memory T cells to survive when antigen is no longer available. Thus, by recruiting TCR-related intracellular molecules into the TRAF2 complex, OX40 provides the T cell with a high level of NF-kappaB activity needed for longevity. |
