anisomycin and Neural-Tube-Defects

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.

Topics: Adaptor Proteins, Signal Transducing; Animals; Anisomycin; Antibody Formation; Antineoplastic Agents; Apoptosis; B-Cell CLL-Lymphoma 10 Protein; B-Lymphocytes; Cell Division; Central Nervous System; Cisplatin; Enzyme Inhibitors; Etoposide; Genes, Lethal; Immunity, Cellular; Lymphocyte Activation; Mice; Mice, Knockout; Neoplasm Proteins; Neural Tube Defects; NF-kappa B; Nucleic Acid Synthesis Inhibitors; Protein Synthesis Inhibitors; Receptors, Antigen; Signal Transduction; Staurosporine; T-Lymphocytes