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A requirement for CARMA1 in TCR-induced NF-κB activation

Nature Immunology volume 3, pages 830835 (2002) | Download Citation

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Abstract

Stimulation of the T cell receptor (TCR) complex initiates multiple signaling cascades that lead to the activation of several transcription factors, including the NF-κB family members. Although various proximal signaling components of the TCR have been intensively studied, the distal components that mediate TCR-induced NF-κB activation remain largely unknown. Using a somatic mutagenesis approach, we cloned a CARMA1-deficient T cell line. Deficiency in CARMA1 (originally known as CARDII) resulted in selectively impaired activation of NF-κB induced by the TCR and a consequent defect in interleukin-2 (IL-2) production. Reconstitution of the CARMA1-deficient cells with CARMA1 fully rescued this signaling defect. Together, our results show that CARMA1 is an essential signaling component that mediates TCR-induced NF-κB activation.

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Acknowledgements

We thank V. Dixit, W. Greene, S.-C. Sun, J. Tschop, M. Yan and A. Weiss for reagents; M. Lindermann and S. Gaffen for help in the HT-2 cell proliferation assays; and J. Hay and S. Gaffen for critical reading of this manuscript.

Author information

Author notes

    • Donghai Wang
    •  & Yun You

    These authors contributed equally to this work.

Affiliations

  1. Department of Microbiology, School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, NY 14214, USA.

    • Donghai Wang
    • , Yun You
    • , Sara M. Case
    •  & Xin Lin
  2. Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

    • Linda M. McAllister-Lucas
    •  & Gabriel Nuñez
  3. Millennium Pharmaceuticals, Inc., Cambridge, MA 02139, USA.

    • Lin Wang
    • , Peter S. DiStefano
    •  & John Bertin

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Xin Lin.

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DOI

https://doi.org/10.1038/ni824

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