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Science 316 (5825): 754-758

Copyright © 2007 by the American Association for the Advancement of Science

Regulation of NF-{kappa}B Activation in T Cells via Association of the Adapter Proteins ADAP and CARMA1

Ricardo B. Medeiros,1* Brandon J. Burbach,1* Kristen L. Mueller,1 Rupa Srivastava,1 James J. Moon,2 Sarah Highfill,1 Erik J. Peterson,3 Yoji Shimizu1{dagger}

Abstract: The adapter protein ADAP regulates T lymphocyte adhesion and activation. We present evidence for a previously unrecognized function for ADAP in regulating T cell receptor (TCR)–mediated activation of the transcription factor NF-{kappa}B. Stimulation of ADAP-deficient mouse T cells with antibodies to CD3 and CD28 resulted in impaired nuclear translocation of NF-{kappa}B, a reduced DNA binding, and delayed degradation and decreased phosphorylation of I{kappa}B (inhibitor of NF-{kappa}B). TCR-stimulated assembly of the CARMA1–BCL-10–MALT1 complex was substantially impaired in the absence of ADAP. We further identified a region of ADAP that is required for association with the CARMA1 adapter and NF-{kappa}B activation but is not required for ADAP-dependent regulation of adhesion. These findings provide new insights into ADAP function and the mechanism by which CARMA1 regulates NF-{kappa}B activation in T cells.

1 Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
2 Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
3 Department of Medicine, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: shimi002{at}umn.edu


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