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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2011-2-2
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pubmed:abstractText |
The Carma1-Bcl10-Malt1 (CBM) complex bridges T-cell receptor (TCR) signalling to the canonical I?B kinase (IKK)/NF-?B pathway. NF-?B activation is triggered by PKC?-dependent phosphorylation of Carma1 after TCR/CD28 co-stimulation. PKC?-phosphorylated Carma1 was suggested to function as a molecular scaffold that recruits preassembled Bcl10-Malt1 complexes to the membrane. We have identified the serine-threonine protein phosphatase PP2A regulatory subunit A? (PPP2R1A) as a novel interaction partner of Carma1. PPP2R1A is associated with Carma1 in resting as well as activated T cells in the context of the active CBM complex. By siRNA-mediated knockdown and in vitro dephosphorylation, we demonstrate that PP2A removes PKC?-dependent phosphorylation of Ser645 in Carma1, and show that maintenance of this phosphorylation is correlated with increased T-cell activation. As a result of PP2A inactivation, we find that enhanced Carma1 S645 phosphorylation augments CBM complex formation, NF-?B activation and IL-2 or IFN-? production after stimulation of Jurkat T cells or murine Th1 cells. Thus, our data define PP2A-mediated dephosphorylation of Carma1 as a critical step to limit T-cell activation and effector cytokine production.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CARD Signaling Adaptor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CARD11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Guanylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Multiprotein Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/PPP2R1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 2
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1460-2075
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pubmed:author |
pubmed-author:BeiskerWolfgangW,
pubmed-author:DüwelMichaelM,
pubmed-author:DemskiKatrinK,
pubmed-author:EitelhuberAndrea CAC,
pubmed-author:HadianKamyarK,
pubmed-author:HeissmeyerVigoV,
pubmed-author:KrappmannDanielD,
pubmed-author:KurosakiTomohiroT,
pubmed-author:SchimmackGiselaG,
pubmed-author:ShinoharaHisaakiH,
pubmed-author:WarthSebastianS
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pubmed:issnType |
Electronic
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pubmed:day |
2
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
594-605
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pubmed:meshHeading |
pubmed-meshheading:21157432-Animals,
pubmed-meshheading:21157432-CARD Signaling Adaptor Proteins,
pubmed-meshheading:21157432-CD4-Positive T-Lymphocytes,
pubmed-meshheading:21157432-DNA Primers,
pubmed-meshheading:21157432-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:21157432-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:21157432-Flow Cytometry,
pubmed-meshheading:21157432-Gene Knockdown Techniques,
pubmed-meshheading:21157432-Guanylate Cyclase,
pubmed-meshheading:21157432-HEK293 Cells,
pubmed-meshheading:21157432-Humans,
pubmed-meshheading:21157432-Immunoprecipitation,
pubmed-meshheading:21157432-Jurkat Cells,
pubmed-meshheading:21157432-Luciferases,
pubmed-meshheading:21157432-Lymphocyte Activation,
pubmed-meshheading:21157432-Mice,
pubmed-meshheading:21157432-Mice, Transgenic,
pubmed-meshheading:21157432-Multiprotein Complexes,
pubmed-meshheading:21157432-NF-kappa B,
pubmed-meshheading:21157432-Phosphorylation,
pubmed-meshheading:21157432-Protein Phosphatase 2,
pubmed-meshheading:21157432-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:21157432-Transduction, Genetic
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pubmed:year |
2011
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pubmed:articleTitle |
Dephosphorylation of Carma1 by PP2A negatively regulates T-cell activation.
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pubmed:affiliation |
Department of Cellular Signal Integration, Helmholtz Zentrum München-German Research Center for Environmental Health, Institute of Toxicology, Neuherberg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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