Abstract
CARMA proteins are scaffold molecules that contain a caspase recruitment domain and a membrane-associated guanylate kinase-like domain. CARMA1 plays a critical role in mediating activation of the NFkappaB transcription factor following antigen receptor stimulation of both B and T lymphocytes. However, the biochemical mechanism by which CARMA1 regulates activation of NFkappaB remains to be determined. Here we have shown that CARMA1 and CARMA3 physically associate with Ikappa kinase gamma/NFkappaB essential modulator (IkappaKgamma-NEMO) in lymphoid and non-lymphoid cells. CARMA1 participates to an inducible large molecular complex that contains IkappaKgamma/NEMO, Bcl10, and IkappaKalpha/beta kinases. Expression of the NEMO-binding region of CARMA3 exerts a dominant negative effect on Bcl10-mediated activation of NFkappaB. Thus, our results provide direct evidence for physical and functional interaction between CARMA and the IkappaK complex and offer a biochemical framework to understand the molecular activities controlled by CARMA-1, -2, and -3 and Bcl10.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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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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B-Lymphocytes / metabolism
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CARD Signaling Adaptor Proteins
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Cell Line
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Cell Membrane / metabolism
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Chromatography, Gel
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Gene Library
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Genes, Dominant
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Guanylate Cyclase / chemistry
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Guanylate Cyclase / metabolism*
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Humans
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I-kappa B Kinase
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Immunoblotting
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Jurkat Cells
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Luciferases / metabolism
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Lymphocytes / metabolism
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Membrane Proteins / chemistry
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Membrane Proteins / metabolism*
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NF-kappa B / metabolism*
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Neoplasm Proteins / metabolism
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Nucleoside-Phosphate Kinase / chemistry
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Nucleoside-Phosphate Kinase / metabolism*
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Plasmids / metabolism
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Precipitin Tests
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Protein Binding
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Protein Serine-Threonine Kinases / metabolism*
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Protein Structure, Tertiary
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Recombinant Proteins / chemistry
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T-Lymphocytes / metabolism
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Transcription, Genetic
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Two-Hybrid System Techniques
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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CARD10 protein, human
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Membrane Proteins
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NF-kappa B
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Neoplasm Proteins
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Recombinant Proteins
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Luciferases
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Protein Serine-Threonine Kinases
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CHUK protein, human
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I-kappa B Kinase
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IKBKB protein, human
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IKBKE protein, human
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Nucleoside-Phosphate Kinase
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CARD11 protein, human
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Guanylate Cyclase