Abstract
The T-cell specific adapter protein (TSAd) encoded by the SH2D2A gene is up-regulated in activated human CD4+ T-cells in a cAMP-dependent manner. Expression of SH2D2A is important for proper activation of T-cells. Here, we show that SH2D2A expression is regulated both at the transcriptional and translational level. cAMP signaling alone induces TSAd-mRNA expression but fails to induce increased TSAd protein levels. By contrast, TCR engagement provides signals for both TSAd transcription and translation. We further show that cAMP signaling can prime T-cells for a more prompt expression of TSAd protein upon TCR stimulation. Our study thus points to a novel mechanism for how cAMP signaling may modulate T-cell activation through transcriptional priming of resting cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics*
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CD3 Complex / immunology
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / metabolism*
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Cross-Priming / drug effects
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Cross-Priming / immunology
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Cyclic AMP / metabolism
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cytoplasm / drug effects
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Cytoplasm / metabolism
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Gene Expression Regulation* / drug effects
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Humans
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Isoquinolines / pharmacology
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Models, Immunological
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Protein Biosynthesis* / drug effects
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RNA Transport / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Antigen, T-Cell / immunology
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Signal Transduction / drug effects
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Sulfonamides / pharmacology
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Transcription, Genetic* / drug effects
Substances
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Adaptor Proteins, Signal Transducing
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CD3 Complex
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Isoquinolines
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RNA, Messenger
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Receptors, Antigen, T-Cell
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SH2D2A protein, human
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Sulfonamides
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide