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CARMA1 is a critical lipid raft–associated regulator of TCR-induced NF-κB activation

Nature Immunologyvolume 3pages836843 (2002) | Download Citation

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Abstract

CARMA1 is a lymphocyte-specific member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, which coordinate signaling pathways emanating from the plasma membrane. CARMA1 interacts with Bcl10 via its caspase-recruitment domain (CARD). Here we investigated the role of CARMA1 in T cell activation and found that T cell receptor (TCR) stimulation induced a physical association of CARMA1 with the TCR and Bcl10. We found that CARMA1 was constitutively associated with lipid rafts, whereas cytoplasmic Bcl10 translocated into lipid rafts upon TCR engagement. A CARMA1 mutant, defective for Bcl10 binding, had a dominant-negative (DN) effect on TCR-induced NF-κB activation and IL-2 production and on the c-Jun NH2-terminal kinase (Jnk) pathway when the TCR was coengaged with CD28. Together, our data show that CARMA1 is a critical lipid raft–associated regulator of TCR-induced NF-κB activation and CD28 costimulation–dependent Jnk activation.

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Acknowledgements

Supported by grants from the Swiss Cancer League (to M. T. and J. T.) and by the Swiss Academy of Medical Sciences (to O. G). C. B. and D. L. were supported by grants from the Swiss National Science Foundation and the Giorgi Cavaglieri Foundation; S. V. was supported by grants from La Ligue contre le Cancer, La Fondation pour la Recherche Médicale and the Giorgio Cavaglieri Foundation. We thank S. Levrand for technical assistance, P. Zaech for help with FACS analysis and K. Burns, F. Martinon and M. Thurau for critical review of the manuscript.

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Author notes

  1. Olivier Gaide and Benoît Favier: These authors contributed equally to this work.

Affiliations

  1. Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, Epalinges, CH-1066, Switzerland

    • Olivier Gaide
    • , Daniel F. Legler
    • , David Bonnet
    • , Brian Brissoni
    • , Claude Bron
    • , Jürg Tschopp
    •  & Margot Thome
  2. INSERM U563, Institut Claude de Préval, CHU Purpan, Toulouse, F-31059, France

    • Benoît Favier
    •  & Salvatore Valitutti

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The authors declare no competing financial interests.

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Correspondence to Margot Thome.

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https://doi.org/10.1038/ni830

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