Requirement for Caspase-8 in NF-κB Activation by Antigen Receptor
| Autor: | Janet K. Dale, Stephen Straus, Razqallah Hakem, Lixin Zheng, Helen C. Su, Nicolas Bidère, Alan Cubre, Leonardo Salmena, Keiko Sakai, Michael J. Lenardo |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Lipopolysaccharides
T-Lymphocytes Receptors Antigen T-Cell Apoptosis Receptors Cell Surface IκB kinase Cysteine Proteinase Inhibitors Protein Serine-Threonine Kinases Lymphocyte Activation Transfection Caspase 8 Amino Acid Chloromethyl Ketones Cell Line Mice Animals Humans Phosphorylation Receptor Transcription factor Protein Kinase C Caspase Cell Nucleus B-Lymphocytes Toll-like receptor Membrane Glycoproteins Multidisciplinary biology Receptors IgG Toll-Like Receptors Immunologic Deficiency Syndromes NF-kappa B Transcription Factor RelA I-Kappa-B Kinase Molecular biology Immunity Innate I-kappa B Kinase Cell biology Isoenzymes Killer Cells Natural Toll-Like Receptor 4 Protein Kinase C-theta Caspases Mutation biology.protein Signal transduction Signal Transduction |
| Zdroj: | Science. 307:1465-1468 |
| ISSN: | 1095-9203 0036-8075 |
| Popis: | Caspase-8, a proapoptotic protease, has an essential role in lymphocyte activation and protective immunity. We show that caspase-8 deficiency (CED) in humans and mice specifically abolishes activation of the transcription factor nuclear factor kappaB (NF-kappaB) after stimulation through antigen receptors, Fc receptors, or Toll-like receptor 4 in T, B, and natural killer cells. Caspase-8 also causes the alphabeta complex of the inhibitor of NF-kappaB kinase (IKK) to associate with the upstream Bcl10-MALT1 (mucosa-associated lymphatic tissue) adapter complex. Recruitment of the IKKalpha, beta complex, its activation, and the nuclear translocation of NF-kappaB require enzyme activity of full-length caspase-8. These findings thus explain the paradoxical association of defective apoptosis and combined immunodeficiency in human CED. |
| Databáze: | OpenAIRE |
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