CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B

The caspase recruitment domain (CARD) is a protein-binding module that medi ates the assembly of CARD-containing proteins into apoptosis and NF-kappaB signaling complexes. We report here that CARD protein II (CARD11) and CARD protein 14 (CARD14) are novel CARD-containing proteins that belong to the m embrane associated guanylate kinase (MAGUK) family, a class of proteins tha t functions as molecular scaffolds for the assembly of multiprotein complex es at specialized regions of the plasma membrane. CARD11 and CARD14 have ho mologous structures consisting of an N-terminal CARD domain, a central coil ed-coil domain, and a C-terminal tripartite domain comprised of a PDZ domai n, an Src homology 3 domain, and a GUK domain with homology to guanylate ki nase, The CARD domains of both CARD11 and CARD14 associate specifically wit h the CARD domain of BCL10, a signaling protein that activates NF-kappaB th rough the I kappaB kinase complex in response to upstream stimuli. When exp ressed in cells, CARD11 and CARD14 activate NF-kappaB and induce the phosph orylation of BCL10. These findings suggest that CARD11 and CARD14 are novel MAGUK family members that function as upstream activators of BCL10 and NF- kappaB signaling.