Extracellular HIV‐1 Tat protein activates phosphatidylinositol 3‐ and Akt/PKB kinases in CD4+ T lymphoblastoid Jurkat cells

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Abstract
The biological basis for the pleiotropic activity of extracellular human immunodeficiency virus (HIV)‐1 Tat protein on lymphoid T cell survival is not well understood. We have here demonstrated that the addition in culture of 0.1–10 nM Tat protein to 36‐h serum‐starved lymphoblastoid Jurkat T cells rapidly stimulates the catalytic activity of phosphatidylinositol 3‐kinase (PI 3‐K). The peak of activation was observed 30 min after Tat addition. Extracellular Tat also stimulated the catalytic activity of the Akt/PKB kinase, a major target of PI 3‐K lipid products. Pretreatment of serum‐starved Jurkat cells with 100 nM wortmannin (WT) or 10 μM LY294002, two unrelated pharmacological inhibitors of PI 3‐K, markedly suppressed the catalytic activity of both PI 3‐K and Akt/PKB in Jurkat cells. Moreover, at low concentrations (0.1–1 nM), extracellular Tat showed a small but reproducible protection of Jurkat cells from apoptosis induced by serum deprivation (p < 0.05), while the combination of Tat plus 100 nM WT significantly (p < 0.05) increased the percentage of apoptosis with respect to cells left untreated or treated with Tat alone. Taken together, these data suggest that the anti‐apoptotic activity of low concentrations of Tat protein on Jurkat cells is mediated by a PI 3‐kinase/Akt pathway.