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

Ricardo B. Medeiros, Brandon J. Burbach, Kristen L. Mueller, Rupa Srivastava, James J. Moon, Sarah Highfill, Erik J. Peterson, Yoji Shimizu

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

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

Original languageEnglish (US)
Pages (from-to)754-758
Number of pages5
JournalScience
Volume316
Issue number5825
DOIs
StatePublished - May 4 2007

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