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CD43-mediated Signals Induce DNA Binding Activity of AP-1, NF-AT, and NFκB Transcription Factors in Human T Lymphocytes

Although numerous reports document a role for CD43 in T cell signaling, the direct participation of this molecule in cell activation has been questioned. In this study we show that CD43 ligation on human normal peripheral T cells was sufficient to induce interleukin-2, CD69, and CD40-L gene expressi...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-10, Vol.275 (40), p.31460
Main Authors: M. Angélica Santana, Gustavo Pedraza-Alva, Norma Olivares-Zavaleta, Vicente Madrid-Marina, Vaclav Horejsi, Steven J. Burakoff, Yvonne Rosenstein
Format: Article
Language:English
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Summary:Although numerous reports document a role for CD43 in T cell signaling, the direct participation of this molecule in cell activation has been questioned. In this study we show that CD43 ligation on human normal peripheral T cells was sufficient to induce interleukin-2, CD69, and CD40-L gene expression, without requiring signals provided by additional receptor molecules. This response was partially inhibited by cyclosporin A and staurosporine, suggesting the participation of both the Ca 2+ and the protein kinase C pathways in CD43 signaling. Consistent with the transient CD43-dependent intracellular Ca 2+ peaks reported by others, signals generated through the CD43 molecule resulted in the induction of NF-AT DNA binding activity. CD43-dependent signals resulted also in AP-1 and NFκB activation, probably as a result of protein kinase C involvement. AP-1 complexes bound to the AP-1 sequence contained c-Jun, and those bound to the NF-AT-AP-1 composite site contained c-Jun and Fos. NFκB complexes containing p65 could be found as early as 1 h after CD43 cross-linking, suggesting that CD43 participates in early events of T cell activation. The induction of the interleukin-2, CD69, and CD-40L genes and the participation of AP-1, NF-AT, and NFκB in the CD43-mediated signaling cascade implicate an important role for this molecule in the regulation of gene expression and cell function.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M005231200