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PMID:11163238
| Citation |
Ruland, J, Duncan, GS, Elia, A, del Barco Barrantes, I, Nguyen, L, Plyte, S, Millar, DG, Bouchard, D, Wakeham, A, Ohashi, PS and Mak, TW (2001) Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure. Cell 104:33-42 |
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| 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. |
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| Keywords |
Adaptor Proteins, Signal Transducing; Animals; Anisomycin/pharmacology; Antibody Formation/immunology; Antineoplastic Agents/pharmacology; Apoptosis/drug effects; Apoptosis/immunology; Apoptosis/radiation effects; 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 |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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