title: Bimp1, a MAGUK family member linking protein kinase C activation to Bcl10-mediated NF-kappaB induction.
abstract: 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 characterize Bimp1, a new signaling protein that binds Bcl10 and activates NF-kappaB. Bimp1-mediated NF-kappaB activation requires Bcl10 and IkappaB kinases, indicating that Bimp1 acts upstream of these mediators. Bimp1, Bcl10, and MALT1 form a ternary complex, with Bcl10 bridging the Bimp1/MALT1 interaction. 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.
authors.affiliation: Department of Pediatrics and Communicable Diseases, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: McAllister-Lucas
authors.forename: N
authors.initials: N
authors.lastname: Inohara
authors.forename: P C
authors.initials: PC
authors.lastname: Lucas
authors.forename: J
authors.initials: J
authors.lastname: Ruland
authors.forename: A
authors.initials: A
authors.lastname: Benito
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: F F
authors.initials: FF
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Yamaoka
authors.forename: I M
authors.initials: IM
authors.lastname: Verma
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
authors.forename: G
authors.initials: G
authors.lastname: Núñez
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000074018:B-Cell CLL-Lymphoma 10 Protein; D020169:Caspases; D018076:DNA, Complementary / Q000032:analysis; D004789:Enzyme Activation; D051528:Guanylate Kinases; D006801:Humans; D051550:I-kappa B Kinase; D018442:Lymphoma, B-Cell, Marginal Zone; D008969:Molecular Sequence Data; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D009703:Nucleoside-Phosphate Kinase / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D018076:DNA, Complementary; D016328:NF-kappa B; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D011493:Protein Kinase C; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein