Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure

Cell. 2001 Jan 12;104(1):33-42. doi: 10.1016/s0092-8674(01)00189-1.

Abstract

Bcl10, a CARD-containing protein identified from the t(1;14)(p22;q32) breakpoint in MALT lymphomas, has been shown to induce apoptosis and activate NF-kappaB in vitro. We show that one-third of bcl10-/- embryos developed exencephaly, leading to embryonic lethality. Surprisingly, bcl10-/- cells retained susceptibility to various apoptotic stimuli in vivo and in vitro. However, surviving bcl10-/- mice were severely immunodeficient and bcl10-/- lymphocytes are defective in antigen receptor or PMA/Ionomycin-induced activation. Early tyrosine phosphorylation, MAPK and AP-1 activation, and Ca2+ signaling were normal in mutant lymphocytes, but antigen receptor-induced NF-kappaB activation was absent. Thus, Bcl10 functions as a positive regulator of lymphocyte proliferation that specifically connects antigen receptor signaling in B and T cells to NF-kappaB activation.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Anisomycin / pharmacology
  • Antibody Formation / immunology
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Apoptosis / radiation effects
  • B-Cell CLL-Lymphoma 10 Protein
  • B-Lymphocytes / immunology
  • Cell Division / immunology
  • Central Nervous System / abnormalities*
  • Central Nervous System / physiology
  • Cisplatin / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Etoposide / pharmacology
  • Genes, Lethal / immunology
  • Immunity, Cellular / immunology
  • Lymphocyte Activation / physiology
  • Mice
  • Mice, Knockout
  • NF-kappa B / immunology
  • NF-kappa B / metabolism*
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / immunology*
  • Neoplasm Proteins / metabolism
  • Neural Tube Defects / immunology
  • Neural Tube Defects / physiopathology*
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Protein Synthesis Inhibitors / pharmacology
  • Receptors, Antigen / immunology
  • Receptors, Antigen / metabolism*
  • Signal Transduction / immunology
  • Staurosporine / pharmacology
  • T-Lymphocytes / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • B-Cell CLL-Lymphoma 10 Protein
  • Bcl10 protein, mouse
  • Enzyme Inhibitors
  • NF-kappa B
  • Neoplasm Proteins
  • Nucleic Acid Synthesis Inhibitors
  • Protein Synthesis Inhibitors
  • Receptors, Antigen
  • Anisomycin
  • Etoposide
  • Staurosporine
  • Cisplatin