| Autor: |
Briggs, S D, Scholtz, B, Jacque, J M, Swingler, S, Stevenson, M, Smithgall, T E |
| Zdroj: |
Journal of Biological Chemistry; July 2001, Vol. 276 Issue: 27 p25605-11, 7p |
| Abstrakt: |
Human immunodeficiency virus Nef is a small myristylated protein that plays a critical role in AIDS progression. Nef binds with high affinity to the SH3 domain of the myeloid-restricted tyrosine kinase Hck in vitro, identifying this Src-related kinase as a possible cellular target for Nef in macrophages. Here we show that Nef activates endogenous Hck in the granulocyte-macrophage colony-stimulating factor-dependent myeloid cell line, TF-1. Unexpectedly, Nef induced cytokine-independent TF-1 cell outgrowth and constitutive activation of the Stat3 transcription factor. Induction of survival required the Nef SH3 binding and membrane-targeting motifs and was blocked by dominant-negative Stat3 mutants. Nef also stimulated Stat3 activation in primary human macrophages, providing evidence for Stat3 as a Nef effector in a target cell for human immunodeficiency virus. |
| Databáze: |
Supplemental Index |
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