Extracellular HIV-1 tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4+ T lymphoblastoid jurkat cells Academic Article uri icon

Overview

MeSH Major

  • CD4-Positive T-Lymphocytes
  • Extracellular Space
  • Gene Products, tat
  • Phosphatidylinositol 3-Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins

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 microM 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.

publication date

  • November 1997

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1002/eji.1830271110

PubMed ID

  • 9394803

Additional Document Info

start page

  • 2805

end page

  • 11

volume

  • 27

number

  • 11