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

J Biol Chem. 2001 Aug 17;276(33):30589-97. doi: 10.1074/jbc.M103824200. Epub 2001 May 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • B-Cell CLL-Lymphoma 10 Protein
  • Caspases
  • DNA, Complementary / analysis
  • Enzyme Activation
  • Guanylate Kinases
  • Humans
  • I-kappa B Kinase
  • Lymphoma, B-Cell, Marginal Zone*
  • Molecular Sequence Data
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • NF-kappa B / biosynthesis*
  • Neoplasm Proteins / metabolism
  • Neoplasm Proteins / physiology*
  • Nucleoside-Phosphate Kinase / physiology*
  • Protein Kinase C / physiology*
  • Protein-Serine-Threonine Kinases / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • B-Cell CLL-Lymphoma 10 Protein
  • BCL10 protein, human
  • DNA, Complementary
  • NF-kappa B
  • Neoplasm Proteins
  • Protein-Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • Protein Kinase C
  • Nucleoside-Phosphate Kinase
  • Guanylate Kinases
  • Caspases
  • MALT1 protein, human
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein

Associated data

  • GENBANK/AF363456
  • GENBANK/AF363457