Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF-kappa B activation

Bdl10, a caspase recruitment domain (CARD)containing protein identified fro m a breakpoint in mucosa-associated lymphoid tissue (MALT) B lymphomas, is essential for antigen-receptor-mediated nuclear factor kappaB (NF-kappaB) a ctivation in lymphocytes. We have identified a novel CARD-containing protei n and interaction partner of Bcl10, named Carma1, Carma1 is predominantly e xpressed in lymphocytes and represents a new member of the membrane-associa ted guanylate kinase family. Carma1 binds Bcl10 via its CARD motif and indu ces translocation of Bcl10 from the cytoplasm into perinuclear structures. Moreover, expression of Carma1 induces phosphorylation of Bcl10 and activat ion of the transcription factor NF-kappaB, We propose that Carma1 is a cruc ial component of a novel Bct10-dependent signaling pathway in T-cells that leads to tbe activation of NF-kappaB. (C) 2001 Federation of European Bioch emical Societies. Published by Elsevier Science B.V. All rights reserved.