Bimp1, a MAGUK family member linking protein kinase C activation to Bcl10-mediated NF-kappaB 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 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.
McAllister-Lucas
L M
LM
Department of Pediatrics and Communicable Diseases, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Inohara
N
N
Lucas
P C
PC
Ruland
J
J
Benito
A
A
Li
Q
Q
Chen
S
S
Chen
F F
FF
Yamaoka
S
S
Verma
I M
IM
Mak
T W
TW
Núñez
G
G
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
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