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.
Mesh Terms:
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
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
J. Biol. Chem.
Date: Aug. 13, 2004
PubMed ID: 15184390
View in: Pubmed Google Scholar
Download Curated Data For This Publication
146326
Switch View:
- Interactions 11