title: Antigen-independent signalosome of CARMA1, PKCθ, and TNF receptor-associated factor 2 (TRAF2) determines NF-κB signaling in T cells.
abstract: NF-κB activation is essential for T-cell responses, and costimulatory molecules in the TNF receptor (TNFR) superfamily are viewed as a major source of this signal. Although the TNFR family recruits TNFR-associated factor (TRAF) molecules leading to IKKα/β/γ activation, it is not clear whether simple binding of TRAFs explains why they are such strong activators of NF-κB and so important for T-cell immunity. We now show that one TNFR family member, OX40 (CD134), after ligation by OX40L, assembles a unique complex that not only contains TRAF2, RIP, and IKKα/β/γ but also CARMA1, MALT1, BCL10, and PKC, molecules previously shown to regulate NF-κB activation through the T-cell receptor (TCR). The OX40 signalosome is formed in membrane microdomains irrespective of TCR engagement, and strongly promotes NF-κB activation only if CARMA1 and PKC are recruited. This NF-κB signal allows effector/memory T cells to survive when antigen is no longer available. Thus, by recruiting TCR-related intracellular molecules into the TRAF2 complex, OX40 provides the T cell with a high level of NF-κB activity needed for longevity.
authors.affiliation: Divisions of Molecular Immunology and Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Takanori
authors.initials: T
authors.lastname: So
authors.forename: Pejman
authors.initials: P
authors.lastname: Soroosh
authors.forename: So-Young
authors.initials: SY
authors.lastname: Eun
authors.forename: Amnon
authors.initials: A
authors.lastname: Altman
authors.forename: Michael
authors.initials: M
authors.lastname: Croft
mesh_terms: D000818:Animals; D015153:Blotting, Western; D053468:CARD Signaling Adaptor Proteins / Q000276:immunology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D047468:Immunoprecipitation; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D046912:Multiprotein Complexes / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011493:Protein Kinase C / Q000276:immunology / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D053262:Receptors, OX40 / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D047992:TNF Receptor-Associated Factor 2 / Q000276:immunology / Q000378:metabolism*; D014461:Ultracentrifugation
chemical_list: D053468:CARD Signaling Adaptor Proteins; C496467:Card11 protein, mouse; D007527:Isoenzymes; D046912:Multiprotein Complexes; D016328:NF-kappa B; D053262:Receptors, OX40; D047992:TNF Receptor-Associated Factor 2; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta