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CARD11 Mediates Factor-specific Activation of NF-kappaB by the T Cell Receptor Complex

Overview
Journal EMBO J
Date 2002 Oct 3
PMID 12356734
Citations 99
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Abstract

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.

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References
1.
Pomerantz J, Baltimore D . NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. EMBO J. 1999; 18(23):6694-704. PMC: 1171732. DOI: 10.1093/emboj/18.23.6694. View

2.
Zhang Q, Siebert R, Yan M, Hinzmann B, Cui X, Xue L . Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32). Nat Genet. 1999; 22(1):63-8. DOI: 10.1038/8767. View

3.
Morgan J, Yin Y, Borowsky A, Kuo F, Nourmand N, Koontz J . Breakpoints of the t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma lie within or near the previously undescribed gene MALT1 in chromosome 18. Cancer Res. 2000; 59(24):6205-13. View

4.
Sun Z, Arendt C, Ellmeier W, Schaeffer E, Sunshine M, Gandhi L . PKC-theta is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes. Nature. 2000; 404(6776):402-7. DOI: 10.1038/35006090. View

5.
Karin M, Ben-Neriah Y . Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol. 2000; 18:621-63. DOI: 10.1146/annurev.immunol.18.1.621. View