| First Author | Pomerantz JL | Year | 2002 |
| Journal | EMBO J | Volume | 21 |
| Issue | 19 | Pages | 5184-94 |
| PubMed ID | 12356734 | Mgi Jnum | J:84961 |
| Mgi Id | MGI:2670943 | Doi | 10.1093/emboj/cdf505 |
| Citation | Pomerantz JL, et al. (2002) CARD11 mediates factor-specific activation of NF-kappaB by the T cell receptor complex. EMBO J 21(19):5184-94 |
| abstractText | NF-kappaB is a critical target of signaling downstream of the T cell receptor (TCR) complex, but how TCR signaling activates NF-kappaB is poorly understood. We have developed an expression cloning strategy that can identify catalytic and noncatalytic molecules that participate in different pathways of NF-kappaB activation. Screening of a mouse thymus cDNA library yielded CARD11, a membrane-associated guanylate kinase (MAGUK) family member containing CARD, PDZ, SH3 and GUK domains. Using a CARD-deleted variant of CARD11 and RNA interference (RNAi), we demonstrate that CARD11 mediates NF-kappaB activation by alphaCD3/alphaCD28 cross-linking and PMA/ionomycin treatment, but not by TNFalpha or dsRNA. CARD11 is not required for TCR-mediated induction of NFAT or AP-1. CARD11 functions upstream of the IkappaB-kinase (IKK) complex and cooperates with Bcl10 in a CARD domain-dependent manner. RNAi-rescue experiments suggest that the CARD, coiled-coil, SH3 and GUK domains of CARD11 are critical for its signaling function. These results implicate CARD11 in factor- specific activation of NF-kappaB by the TCR complex and establish a role for a MAGUK family member in antigen receptor signaling. |
