Regulation of NF-κB activation in T cells via association of the adapter proteins ADAP and CARMA1

Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Science (Impact Factor: 33.61). 06/2007; 316(5825):754-8. DOI: 10.1126/science.1137895
Source: PubMed


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-kappaB. Stimulation of ADAP-deficient mouse T cells with antibodies to CD3 and CD28 resulted in impaired nuclear translocation of NF-kappaB, a reduced DNA binding, and delayed degradation and decreased phosphorylation of IkappaB (inhibitor of NF-kappaB). 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-kappaB 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-kappaB activation in T cells.

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Available from: Ricardo De Medeiros, May 07, 2015
    • ") whereas RIAM activates NFAT by controlling the activation of PLC1 (Patsoukis et al., 2009). Along the same line, ADAP has been shown to activate NF-B signaling, an event not directly required for ADAP-SKAP55-dependent regulation of cell adhesion (Medeiros et al., 2007), emphasizing the fact that components of inside-out signaling pathways can influence distinct TCR signaling events beyond their adhesion function. "
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