title: CD28-costimulation activates cyclic AMP-responsive element-binding protein in T lymphocytes.
abstract: Cyclic AMP-responsive element binding protein (CREB) mediates gene expression in response to cAMP stimulation. The transcriptional activity of CREB depends on both the phosphorylation of Ser133 and the recruitment of cofactor for assembly of transcriptional complex. Extensive Ser133 phosphorylation of CREB was induced during T cell activation. This phosphorylation event is essential for IL-2 gene expression. However, phosphorylation of CREB at Ser133 was not sufficient for transcriptional activity by CREB. The presence of a second signal from CD28, a potent costimulatory molecule on T cells, stimulated CREB-mediated gene expression. CD28, an effective costimulator of T cell activation and IL-2 gene expression, is shown to induce CREB activation in the presence of anti-CD3 or O-tetradecanoylphorbol 13-acetate. These two signals together stimulated a CRE-dependent reporter gene, the proliferating cell nuclear Ag promoter, and transactivation by the GAL4-CREB fusion protein. Thus optimal induction of CREB, similar to the full activation of T lymphocytes, may be mediated by two distinct signal transductions. Using the specific kinase inhibitor, one of the two pathways appeared to involve mitogen-activated protein kinase kinase but not protein kinase C, protein kinase A, or p70 S6 kinase.
authors.affiliation: Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Y P
authors.initials: YP
authors.lastname: Hsueh
authors.forename: H E
authors.initials: HE
authors.lastname: Liang
authors.forename: S Y
authors.initials: SY
authors.lastname: Ng
authors.forename: M Z
authors.initials: MZ
authors.lastname: Lai
mesh_terms: D051697:Activating Transcription Factor 1; D000818:Animals; D018106:CD28 Antigens / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology; D004268:DNA-Binding Proteins; D015870:Gene Expression / Q000235:genetics; D006825:Hybridomas; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases; D010766:Phosphorylation; D011493:Protein Kinase C / Q000494:pharmacology; D011494:Protein Kinases / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000494:pharmacology; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects*; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D051697:Activating Transcription Factor 1; C497100:Atf1 protein, mouse; D018106:CD28 Antigens; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D020929:Mitogen-Activated Protein Kinase Kinases