HIV-1 Nef inhibits a common activation pathway in NIH-3T3 cells
| Autor: | Jon W. Marsh, S K De |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Thapsigargin
viruses Growth factor medicine.medical_treatment T cell virus diseases Bombesin Cell Biology Biology Biochemistry Virology 3T3 cells Cell biology chemistry.chemical_compound medicine.anatomical_structure chemistry Antigen medicine biology.protein Signal transduction Molecular Biology Platelet-derived growth factor receptor |
| Zdroj: | Journal of Biological Chemistry. 269:6656-6660 |
| ISSN: | 0021-9258 |
| Popis: | The human immunodeficiency virus type 1 (HIV-1) Nef is a myristylated 27-kDa, cytoplasmic protein. It is attributed to have suppressive effects on LTR-based expression and T cell activation. Additionally, SIV nef has been shown to possess an essential in vivo function in the development of immunodeficiency. To define the biochemical activity of HIV-1 Nef in a signal transduction pathway, we have transduced murine NIH-3T3 cells with a retroviral nef expression system. In nef-expressing cells, but not in controls, the proliferative response to bombesin and platelet-derived growth factor (PDGF) was eliminated. Analysis of an early signal pathway metabolite, inositol 1,4,5-trisphosphate, following bombesin and PDGF treatment to quiscent cells, revealed that both control and nef-transformed cells displayed similar kinetics of signal formation. Normally, inositol 1,4,5-trisphosphate mediates increase in the cytosolic free Ca2+ ([Ca2+]i). Upon stimulation with bombesin or PDGF, control cells displayed a 2-4-fold increase of [Ca2+]i over the basal level, while the [Ca2+]i response in nef-expressing NIH-3T3 cells was lacking or highly diminished. However, the release of [Ca2+]i from the intracellular store of the nef-expressing cells by an endomembrane Ca2+ ATPase inhibitor, thapsigargin, revealed that these cells contained normal Ca2+ stores. These results suggest a specific, definable biochemical activity for the HIV-1 Nef protein in the context of a well characterized cellular activation pathway. Our results thus define, for the first time, a unique function of Nef that is not limited to an alteration of T cell function or of expression of a T cell surface antigen. |
| Databáze: | OpenAIRE |
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