Publication Date:
2007-05-05
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Medeiros, Ricardo B -- Burbach, Brandon J -- Mueller, Kristen L -- Srivastava, Rupa -- Moon, James J -- Highfill, Sarah -- Peterson, Erik J -- Shimizu, Yoji -- F32 AI063793/AI/NIAID NIH HHS/ -- F32 AI063793-01A1/AI/NIAID NIH HHS/ -- F32AI063793/AI/NIAID NIH HHS/ -- R01AI038474/AI/NIAID NIH HHS/ -- R01AI056016/AI/NIAID NIH HHS/ -- T32DE007288/DE/NIDCR NIH HHS/ -- New York, N.Y. -- Science. 2007 May 4;316(5825):754-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17478723" target="_blank"〉PubMed〈/a〉
Keywords:
Active Transport, Cell Nucleus
;
Adaptor Proteins, Signal Transducing/chemistry/genetics/*metabolism
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Animals
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Antigens, CD28/immunology
;
Antigens, CD3/immunology
;
Apoptosis Regulatory Proteins/*metabolism
;
CARD Signaling Adaptor Proteins/*metabolism
;
Caspases/metabolism
;
Cell Membrane/metabolism
;
Cell Nucleus/metabolism
;
Humans
;
I-kappa B Proteins/metabolism
;
Isoenzymes/metabolism
;
Jurkat Cells
;
Lymphocyte Activation
;
Mice
;
Mutation
;
Neoplasm Proteins/metabolism
;
Protein Kinase C/metabolism
;
Protein Structure, Tertiary
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Receptors, Antigen, T-Cell/immunology
;
Recombinant Fusion Proteins/metabolism
;
Signal Transduction
;
T-Lymphocytes/*immunology/*metabolism
;
Transcription Factor RelA/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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