Regulation of NF-kappaB-dependent lymphocyte activation and development by paracaspase.
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.
Pubmed ID: 14576442 RIS Download
Adaptor Proteins, Signal Transducing | Animals | Antibody Formation | Antigens, CD | B-Lymphocyte Subsets | B-Lymphocytes | Caspases | Cell Differentiation | Cell Division | Cell Survival | Cells, Cultured | Cytokines | Gene Deletion | Gene Targeting | Guanylate Kinase | I-kappa B Kinase | Lymphocyte Activation | Lymphoma, B-Cell, Marginal Zone | Mice | Mice, Inbred C57BL | NF-kappa B | Neoplasm Proteins | Nucleoside-Phosphate Kinase | Phosphorylation | Protein Structure, Tertiary | Protein-Serine-Threonine Kinases | Receptors, Antigen, B-Cell | Receptors, Antigen, T-Cell | Signal Transduction | T-Lymphocyte Subsets | T-Lymphocytes | Transfection