Expression of SH2D2A in T-cells is regulated both at the transcriptional and translational level.
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.
Kolltveit
Kristin Melkevik
KM
The Institute of Oral Biology, University of Oslo, Sognsvannsvn 10, N-0372 Oslo, Norway.
Granum
Stine
S
Aasheim
Hans-Christian
HC
Forsbring
Monika
M
Sundvold-Gjerstad
Vibeke
V
Dai
Ke-Zheng
KZ
Molberg
Oyvind
O
Schjetne
Karoline W
KW
Bogen
Bjarne
B
Shapiro
Virginia S
VS
Johansen
Finn-Eirik
FE
Schenck
Karl
K
Spurkland
Anne
A
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D045142:Cross-Priming / Q000187:drug effects / Q000276:immunology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D018448:Models, Immunological; D014176:Protein Biosynthesis / Q000187:drug effects; D034443:RNA Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D048868:Adaptor Proteins, Signal Transducing; D017252:CD3 Complex; D007546:Isoquinolines; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; C405691:SH2D2A protein, human; D013449:Sulfonamides; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide