Physical and functional interaction of CARMA1 and CARMA3 with Ikappa kinase gamma-NFkappaB essential modulator.
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.
Pubmed ID: 15184390 RIS Download
Adaptor Proteins, Signal Transducing | Apoptosis Regulatory Proteins | B-Lymphocytes | CARD Signaling Adaptor Proteins | Cell Line | Cell Membrane | Chromatography, Gel | Gene Library | Genes, Dominant | Guanylate Cyclase | Humans | I-kappa B Kinase | Immunoblotting | Jurkat Cells | Luciferases | Lymphocytes | Membrane Proteins | NF-kappa B | Neoplasm Proteins | Nucleoside-Phosphate Kinase | Plasmids | Precipitin Tests | Protein Binding | Protein Structure, Tertiary | Protein-Serine-Threonine Kinases | Recombinant Proteins | T-Lymphocytes | Transcription, Genetic | Two-Hybrid System Techniques