Abstract
Ligation of the TCR triggers signaling events leading to the activation of IL-2 gene transcription. We have developed a genetically manipulatable model system that provides a TCR-like set of activation signals in Jurkat T cells. MT Is a membranelocalized, viral oncoprotein that binds signaling proteins implicated in IL-2 gene transcription, including She, phosphatidylinositol 3-kinase(PI3-K), phospholipase C-?1 (PLCyl), and the src-family tyrosine kinases. Our results demonstrate that the MT antigen transiently expressed in Jurkat cells leads to the activation of an IL-2-promoter-driven luciferase reporter construct. Mutants of MT that are unable to associate with She or PI3-K show a dramatic increase in IL-2 promoter activity over wildtype MT; however, reporter activity is absent with a MT mutant that fails to bind PLC-y1. Similar results were obtained with an (NFAT)3-driven luciferase construct. Treatment of wildtype MTexpressing Jurkat cells with the PI3-K inhibitor, wortmannin, enhances both IL-2 promoter- and NFAT-mediated transcription. These results suggest that whereas PLC-γ1 activation is essential for IL-2 gene transcription, PI3-K and She may downmodulate this response.
Original language | English (US) |
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Pages (from-to) | A1027 |
Journal | FASEB Journal |
Volume | 10 |
Issue number | 6 |
State | Published - 1996 |
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics