Regulation of NF-
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
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-
B. Stimulation of
ADAP-deficient mouse T cells with antibodies to CD3 and CD28
resulted in impaired nuclear translocation of NF-
B, a reduced
DNA binding, and delayed degradation and decreased phosphorylation
of I
B (inhibitor of NF-
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-
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-
B activation in T cells.
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.
To whom correspondence should be addressed. E-mail: shimi002{at}umn.edu
