Antigen-independent signalosome of CARMA1, PKCθ, and TNF receptor-associated factor 2 (TRAF2) determines NF-κB signaling in T cells

Takanori So, Pejman Soroosh, So Young Eun, Amnon Altman, Michael Croft

Research output: Contribution to journalArticle

36 Citations (Scopus)

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 PKCθ, 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 PKCθ 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.

Original languageEnglish
Pages (from-to)2903-2908
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number7
DOIs
Publication statusPublished - 2011 Feb 15

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Antigen-independent signalosome of CARMA1, PKCθ, and TNF receptor-associated factor 2 (TRAF2) determines NF-κB signaling in T cells'. Together they form a unique fingerprint.

  • Cite this