Abstract
Paracaspase (MALT1), a member of an evolutionarily conserved superfamily of caspase-like proteins, has been shown to bind and colocalize with the protein Bcl10 in vitro and, because of this association, has been suggested to be involved in the CARMA1-Bcl10 pathway of antigen-induced nuclear factor kappaB (NF-kappaB) activation. We demonstrate that primary T and B lymphocytes from paracaspase-deficient mice are defective in antigen-receptor-induced NF-kappaB activation, cytokine production, and proliferation. Paracaspase acts downstream of Bcl10 to induce NF-kappaB activation and is required for the normal development of B cells, indicating that paracaspase provides the missing link between Bcl10 and activation of the IkappaB kinase complex.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Animals
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Antibody Formation
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Antigens, CD / analysis
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B-Cell CLL-Lymphoma 10 Protein
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / physiology
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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B-Lymphocytes / physiology
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Caspases
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Cell Differentiation
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Cell Division
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Cell Survival
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Cells, Cultured
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Cytokines / metabolism
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Gene Deletion
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Gene Targeting
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Guanylate Kinases
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I-kappa B Kinase
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Lymphocyte Activation*
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Lymphoma, B-Cell, Marginal Zone / chemistry
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Lymphoma, B-Cell, Marginal Zone / metabolism*
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Mice
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Mice, Inbred C57BL
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
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NF-kappa B / metabolism*
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / metabolism*
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Nucleoside-Phosphate Kinase / metabolism
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Phosphorylation
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Protein Serine-Threonine Kinases / metabolism
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Protein Structure, Tertiary
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Receptors, Antigen, B-Cell / metabolism
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Receptors, Antigen, T-Cell / metabolism
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Signal Transduction
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / physiology
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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T-Lymphocytes / physiology
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Transfection
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, CD
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B-Cell CLL-Lymphoma 10 Protein
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BCL10 protein, human
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Bcl10 protein, mouse
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Cytokines
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NF-kappa B
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Neoplasm Proteins
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Receptors, Antigen, B-Cell
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Receptors, Antigen, T-Cell
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Protein Serine-Threonine Kinases
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Chuk protein, mouse
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I-kappa B Kinase
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Ikbkb protein, mouse
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Ikbke protein, mouse
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Nucleoside-Phosphate Kinase
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Guanylate Kinases
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Caspases
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Malt1 protein, mouse
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein