Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

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

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
CD28 Promotes CD4+ T Cell Clonal Expansion during Infection Independently of Its YMNM and PYAP Motifs.
A. J. Pagan, M. Pepper, H. H. Chu, J. M. Green, and M. K. Jenkins (2012)
J. Immunol. 189, 2909-2917
   Abstract »    Full Text »    PDF »
ADAP Regulates Cell Cycle Progression of T Cells via Control of Cyclin E and Cdk2 Expression through Two Distinct CARMA1-Dependent Signaling Pathways.
R. Srivastava, B. J. Burbach, J. S. Mitchell, A. J. Pagan, and Y. Shimizu (2012)
Mol. Cell. Biol. 32, 1908-1917
   Abstract »    Full Text »    PDF »
The SLP-76 Src Homology 2 Domain Is Required for T Cell Development and Activation.
J. C. Burns, E. Corbo, J. Degen, M. Gohil, C. Anterasian, B. Schraven, G. A. Koretzky, S. Kliche, and M. S. Jordan (2011)
J. Immunol. 187, 4459-4466
   Abstract »    Full Text »    PDF »
The Pleckstrin Homology Domain in the SKAP55 Adapter Protein Defines the Ability of the Adapter Protein ADAP To Regulate Integrin Function and NF-{kappa}B Activation.
B. J. Burbach, R. Srivastava, M. A. Ingram, J. S. Mitchell, and Y. Shimizu (2011)
J. Immunol. 186, 6227-6237
   Abstract »    Full Text »    PDF »
CARMA3 is Crucial for EGFR-Induced Activation of NF-{kappa}B and Tumor Progression.
T. Jiang, B. Grabiner, Y. Zhu, C. Jiang, H. Li, Y. You, J. Lang, M.-C. Hung, and X. Lin (2011)
Cancer Res. 71, 2183-2192
   Abstract »    Full Text »    PDF »
NF-{kappa}B Activation in T Cells Requires Discrete Control of I{kappa}B Kinase {alpha}/{beta} (IKK{alpha}/{beta}) Phosphorylation and IKK{gamma} Ubiquitination by the ADAP Adapter Protein.
R. Srivastava, B. J. Burbach, and Y. Shimizu (2010)
J. Biol. Chem. 285, 11100-11105
   Abstract »    Full Text »    PDF »
Role for ADAP in shear flow-induced platelet mechanotransduction.
A. Kasirer-Friede, Z. M. Ruggeri, and S. J. Shattil (2010)
Blood 115, 2274-2282
   Abstract »    Full Text »    PDF »
Control of {alpha}4{beta}7 Integrin Expression and CD4 T Cell Homing by the {beta}1 Integrin Subunit.
C. C. DeNucci, A. J. Pagan, J. S. Mitchell, and Y. Shimizu (2010)
J. Immunol. 184, 2458-2467
   Abstract »    Full Text »    PDF »
CARMA1 Controls an Early Checkpoint in the Thymic Development of FoxP3+ Regulatory T Cells.
L. L. Molinero, J. Yang, T. Gajewski, C. Abraham, M. A. Farrar, and M.-L. Alegre (2009)
J. Immunol. 182, 6736-6743
   Abstract »    Full Text »    PDF »
Distinct Regulation of Integrin-Dependent T Cell Conjugate Formation and NF-{kappa}B Activation by the Adapter Protein ADAP.
B. J. Burbach, R. Srivastava, R. B. Medeiros, W. E. O'Gorman, E. J. Peterson, and Y. Shimizu (2008)
J. Immunol. 181, 4840-4851
   Abstract »    Full Text »    PDF »
The Protein Kinase C-Responsive Inhibitory Domain of CARD11 Functions in NF-{kappa}B Activation To Regulate the Association of Multiple Signaling Cofactors That Differentially Depend on Bcl10 and MALT1 for Association.
R. R. McCully and J. L. Pomerantz (2008)
Mol. Cell. Biol. 28, 5668-5686
   Abstract »    Full Text »    PDF »
Adhesion and Degranulation-Promoting Adapter Protein (ADAP) Positively Regulates T Cell Sensitivity to Antigen and T Cell Survival.
K. L. Mueller, M. S. Thomas, B. J. Burbach, E. J. Peterson, and Y. Shimizu (2007)
J. Immunol. 179, 3559-3569
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882