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-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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus
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Adaptor Proteins, Signal Transducing / chemistry
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Apoptosis Regulatory Proteins / metabolism*
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B-Cell CLL-Lymphoma 10 Protein
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CARD Signaling Adaptor Proteins / metabolism*
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CD28 Antigens / immunology
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CD3 Complex / immunology
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Caspases / metabolism
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Cell Membrane / metabolism
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Cell Nucleus / metabolism
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Humans
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I-kappa B Proteins / metabolism
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Isoenzymes / metabolism
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Jurkat Cells
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Lymphocyte Activation
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Mice
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
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Mutation
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Neoplasm Proteins / metabolism
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Protein Kinase C / metabolism
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Protein Kinase C-theta
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Protein Structure, Tertiary
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Receptors, Antigen, T-Cell / immunology
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism*
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Transcription Factor RelA / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Apoptosis Regulatory Proteins
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B-Cell CLL-Lymphoma 10 Protein
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Bcl10 protein, mouse
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CARD Signaling Adaptor Proteins
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CD28 Antigens
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CD3 Complex
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Card11 protein, mouse
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Fyb protein, mouse
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I-kappa B Proteins
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Isoenzymes
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Neoplasm Proteins
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Receptors, Antigen, T-Cell
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Recombinant Fusion Proteins
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Rela protein, mouse
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Transcription Factor RelA
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Prkcq protein, mouse
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Protein Kinase C
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Protein Kinase C-theta
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Caspases
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Malt1 protein, mouse
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein