Abstract
CARMA1 is a central regulator of NF-kappaB activation in lymphocytes. CARMA1 and Bcl10 functionally interact and control NF-kappaB signaling downstream of the T-cell receptor (TCR). Computational analysis of expression neighborhoods of CARMA1-Bcl10MALT 1 for enrichment in kinases identified calmodulin-dependent protein kinase II (CaMKII) as an important component of this pathway. Here we report that Ca(2+)/CaMKII is redistributed to the immune synapse following T-cell activation and that CaMKII is critical for NF-kappaB activation induced by TCR stimulation. Furthermore, CaMKII enhances CARMA1-induced NF-kappaB activation. Moreover, we have shown that CaMKII phosphorylates CARMA1 on Ser109 and that the phosphorylation facilitates the interaction between CARMA1 and Bcl10. These results provide a novel function for CaMKII in TCR signaling and CARMA1-induced NF-kappaB activation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Amino Acid Sequence
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism*
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B-Cell CLL-Lymphoma 10 Protein
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CARD Signaling Adaptor Proteins
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Caspases / genetics
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Caspases / metabolism
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Cell Line
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Guanylate Cyclase / genetics
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Guanylate Cyclase / metabolism*
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Humans
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Jurkat Cells
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Lymphocyte Activation
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Molecular Sequence Data
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
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Mutagenesis, Site-Directed
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Phosphorylation
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Receptors, Antigen, T-Cell / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Sequence Homology, Amino Acid
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Signal Transduction
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Adaptor Proteins, Signal Transducing
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Apoptosis Regulatory Proteins
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B-Cell CLL-Lymphoma 10 Protein
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BCL10 protein, human
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CARD Signaling Adaptor Proteins
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NF-kappa B
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Neoplasm Proteins
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Receptors, Antigen, T-Cell
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases
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Caspases
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MALT1 protein, human
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
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CARD11 protein, human
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Guanylate Cyclase