PMID- 21282629
OWN - NLM
STAT- MEDLINE
DCOM- 20110414
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 108
IP  - 7
DP  - 2011 Feb 15
TI  - Antigen-independent signalosome of CARMA1, PKCtheta, and TNF receptor-associated 
      factor 2 (TRAF2) determines NF-kappaB signaling in T cells.
PG  - 2903-8
LID - 10.1073/pnas.1008765108 [doi]
AB  - NF-kappaB 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 IKKalpha/beta/gamma activation, it is not clear whether simple binding of TRAFs 
      explains why they are such strong activators of NF-kappaB 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 
      IKKalpha/beta/gamma but also CARMA1, MALT1, BCL10, and PKC, molecules previously shown to 
      regulate NF-kappaB activation through the T-cell receptor (TCR). The OX40 signalosome 
      is formed in membrane microdomains irrespective of TCR engagement, and strongly 
      promotes NF-kappaB activation only if CARMA1 and PKC are recruited. This NF-kappaB 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-kappaB activity needed for 
      longevity.
FAU - So, Takanori
AU  - So T
AD  - Divisions of Molecular Immunology and Cell Biology, La Jolla Institute for 
      Allergy and Immunology, La Jolla, CA 92037, USA.
FAU - Soroosh, Pejman
AU  - Soroosh P
FAU - Eun, So-Young
AU  - Eun SY
FAU - Altman, Amnon
AU  - Altman A
FAU - Croft, Michael
AU  - Croft M
LA  - eng
GR  - R01 CA035299/CA/NCI NIH HHS/United States
GR  - R01 AI049453/AI/NIAID NIH HHS/United States
GR  - AI49453/AI/NIAID NIH HHS/United States
GR  - R01 CA091837/CA/NCI NIH HHS/United States
GR  - CA35299/CA/NCI NIH HHS/United States
GR  - CA91837/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110131
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (CARD Signaling Adaptor Proteins)
RN  - 0 (Card11 protein, mouse)
RN  - 0 (Isoenzymes)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, OX40)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - EC 2.7.11.13 (Prkcq protein, mouse)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C-theta)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - CARD Signaling Adaptor Proteins/immunology/*metabolism
MH  - Fluorescent Antibody Technique
MH  - Immunoprecipitation
MH  - Isoenzymes/immunology/*metabolism
MH  - Mice
MH  - Multiprotein Complexes/immunology/*metabolism
MH  - NF-kappa B/*metabolism
MH  - Protein Kinase C/immunology/*metabolism
MH  - Protein Kinase C-theta
MH  - Receptors, OX40/immunology/*metabolism
MH  - Signal Transduction/*immunology
MH  - T-Lymphocytes/immunology/*metabolism
MH  - TNF Receptor-Associated Factor 2/immunology/*metabolism
MH  - Ultracentrifugation
PMC - PMC3041086
COIS- The authors declare no conflict of interest.
EDAT- 2011/02/02 06:00
MHDA- 2011/04/16 06:00
PMCR- 2011/08/15
CRDT- 2011/02/02 06:00
PHST- 2011/02/02 06:00 [entrez]
PHST- 2011/02/02 06:00 [pubmed]
PHST- 2011/04/16 06:00 [medline]
PHST- 2011/08/15 00:00 [pmc-release]
AID - 1008765108 [pii]
AID - 201008765 [pii]
AID - 10.1073/pnas.1008765108 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2903-8. doi: 
      10.1073/pnas.1008765108. Epub 2011 Jan 31.