دورية
Grb3-3 Is Up-regulated in HIV-1-infected T-cells and Can Potentiate Cell Activation through NFATc*
| العنوان: | Grb3-3 Is Up-regulated in HIV-1-infected T-cells and Can Potentiate Cell Activation through NFATc* |
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| المؤلفون: | Li, Xuguang, Multon, Marie-Christine, Henin, Yvette, Schweighoffer, Fabien, Venot, Corinne, Josef, Juliana, Zhou, Changhong, LaVecchio, Joyce, Stuckert, Patricia, Raab, Monika, Mhashilkar, Abner, Tocqué, Bruno, Marasco, Wayne A. |
| المصدر: | Journal of Biological Chemistry; October 2000, Vol. 275 Issue: 40 p30925-30933, 9p |
| مستخلص: | The MAPK pathway is required for T-cell activation; however, its role in modulating T-cell function following human immunodeficiency virus type 1 (HIV-1) infection is poorly understood. In this report, we investigated whether Grb3-3, an isoform of the Grb2 (growth factorreceptor-bound protein-2) adaptor molecule that is associated with the MAPK pathway, could be involved. We found that Grb3-3, but not its isoform Grb2, is markedly up-regulated in CD4+peripheral blood mononuclear cells derived from either in vitroHIV-1-infected cultures or HIV-1-infected human subjects. Analysis of HIV-1 gene products indicated that Tat and Nef, both of which have been implicated in modulating T-cell function, can independently induce expression of Grb3-3. By using NFAT/AP-1, AP-1, or NFAT reporter assays, we found that Grb3-3 can potentiate NFAT (but not AP-1) promoter activity in Jurkat T-cells upon engagement of the T-cell receptor and CD28 co-receptor. In addition, potentiation of NFAT by Grb3-3 is substantially suppressed by MEKK1, a kinase that may play an important role in retaining NFAT in the cytoplasm, and by cyclosporin A. Finally, we also found that Grb3-3 potentiates HIV-1 long terminal (LTR) repeat promoter activity following T-cell receptor stimulation, an effect that can be largely suppressed by cyclosporin A. Taken together, this study indicates that Grb3-3 is a cellular factor that can be up-regulated by HIV-1. In addition, Grb3-3 can also function as a positive factor for T-cell activation and, in doing so, may aid in establishing an intracellular environment that can optimally support HIV-1 replication. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 00219258 1083351X |
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| DOI: | 10.1074/jbc.M005535200 |