Bimp1, a MAGUK family member linking protein kinase C activation to Bcl10-mediated NF-kappa B induction

Bcl10 and MALT1, products of distinct chromosomal translocations in mucosa- associated lymphoid tissue lymphoma, cooperate in activating NF-kappaB Mice lacking Bcl10 demonstrate severe immunodeficiency associated with failure of lymphocytes to activate nuclear factor kappaB (NF-kappaB) in response to antigen receptor stimulation and protein kinase C activation. We character ize Bimp1, a new signaling protein that binds Bcl10 and activates NF-kappaB . Bimp1-mediated NF-kappaB activation requires Bcl10 and I kappaB kinases, indicating that Bimp1 acts upstream of these mediators. Bimp1, Bcl10, and M ALT1 form a ternary complex, with Bcl10 bridging the Bimp1/ MALT1 interacti on. A dominant negative Bimp1 mutant inhibits NF-kappaB activation by anti- CD3 ligation, phorbol ester, and protein kinase C expression. These results suggest that Bimp1 links surface receptor stimulation and protein kinase C activation to Bcl10/MALT1, thus leading to NF-kappaB induction.