title: Expression of SH2D2A in T-cells is regulated both at the transcriptional and translational level.
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.
authors.affiliation: The Institute of Oral Biology, University of Oslo, Sognsvannsvn 10, N-0372 Oslo, Norway.
authors.forename: Kristin Melkevik
authors.initials: KM
authors.lastname: Kolltveit
authors.forename: Stine
authors.initials: S
authors.lastname: Granum
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Aasheim
authors.forename: Monika
authors.initials: M
authors.lastname: Forsbring
authors.forename: Vibeke
authors.initials: V
authors.lastname: Sundvold-Gjerstad
authors.forename: Ke-Zheng
authors.initials: KZ
authors.lastname: Dai
authors.forename: Oyvind
authors.initials: O
authors.lastname: Molberg
authors.forename: Karoline W
authors.initials: KW
authors.lastname: Schjetne
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.forename: Virginia S
authors.initials: VS
authors.lastname: Shapiro
authors.forename: Finn-Eirik
authors.initials: FE
authors.lastname: Johansen
authors.forename: Karl
authors.initials: K
authors.lastname: Schenck
authors.forename: Anne
authors.initials: A
authors.lastname: Spurkland
mesh_terms: 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
chemical_list: 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