AP-1 transcriptional activity requires both T-cell receptor-mediated and co-stimulatory signals in primary T lymphocytes.

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Abstract
The transcription factor AP‐1 contributes significantly to the regulation of interleukin‐2 gene transcription during T‐cell activation and may play a role in thymocyte development. To study the regulation of AP‐1 transcriptional activity in primary T‐cells, reporter transgenic mice were generated that express luciferase gene under the control of AP‐1 binding sites. Here, we demonstrate that while protein kinase C activation is sufficient to induce DNA‐binding activity, an additional intracellular calcium increase is required to induce transcriptional activity of AP‐1 in primary mouse T‐cells. Furthermore, transcriptional, but not DNA‐binding, activity of AP‐1 is cyclosporin sensitive and requires tyrosine phosphorylation. This dissociation between DNA‐binding and transcriptional activity is likely due, at least partially, to post‐translational modifications of the AP‐1 complex required for transcriptional activity. Moreover, in addition to these two signals delivered by ligand binding to the T‐cell receptor (TcR) AP‐1 transcriptional activity absolutely requires the presence of a co‐stimulatory signal that can be mediated by the interaction of CD28 with its ligands B7‐1 and B7‐2. Thus, TcR‐mediated and co‐stimulatory signals required for T‐cell activation appear to be integrated, in part, at the level of the regulation of transcriptional activity of AP‐1.