       Document 0638
 DOCN  M9620638
 TI    Exogenous human immunodeficiency virus type-1 Tat protein selectively
       stimulates a phosphatidylinositol-specific phospholipase C nuclear
       pathway in the Jurkat T cell line.
 DT    9602
 AU    Zauli G; Previati M; Caramelli E; Bassini A; Falcieri E; Gibellini D;
       Bertolaso L; Bosco D; Robuffo I; Capitani S; Institute of Human Anatomy,
       University of Ferrara, Italy.
 SO    Eur J Immunol. 1995 Sep;25(9):2695-700. Unique Identifier : AIDSLINE
       MED/96011888
 AB    We investigated the effect of extracellular Tat protein of human
       immunodeficiency virus-type 1 (HIV-1) on the phosphatidylinositol (PI)
       cycle, which represents a major signal transduction pathway in lymphoid
       cells. Recombinant Tat, recombinant HIV-1 p24 and cross-linked anti-CD3
       monoclonal antibody (mAb) were added in culture for 1-60 min to Jurkat
       lymphoblastoid CD4+ T cells. The stimulation of T cell receptor by
       cross-linked anti-CD3 mAb resulted in a rapid increase of the
       phosphatidylinositol-specific phospholipase C (PI-PLC) activity in whole
       cell lysates. On the other hand, Tat protein, either alone or in
       combination with anti-CD3 mAb, showed little effect on the PI turnover
       of whole cell extracts. Tat, however, selectively stimulated a
       nuclear-specific PI-PLC with a peak of activity after 30 min from the
       addition in culture to Jurkat cells. Interestingly, this time
       corresponded to that required for the uptake and nuclear localization of
       recombinant Tat protein, as demonstrated by electron microscope
       immunocytochemistry experiments with anti-Tat mAb. Moreover, exogenous
       Tat reached the nucleus of Jurkat cells in a bioactive form, as shown in
       a HIV-1 long terminal repeat-chloramphenicol acetyl transferase
       transactivation assay. The specific increase of a nuclear PI-PLC
       activity was further demonstrated by the ability of Tat to stimulate PI
       turnover also when added directly to isolated nuclei. As a whole, these
       data demonstrate that Tat selectively stimulates a nuclear
       polyphosphoinositide hydrolysis, which appears to be independent of the
       cellular PI turnover. The relevance of these findings for a better
       understanding of the biological functions of extracellular Tat is
       discussed.
 DE    Biological Transport  Cell Line  Cell Nucleus/METABOLISM/ULTRASTRUCTURE
       Enzyme Activation/DRUG EFFECTS  Gene Products,
       tat/*METABOLISM/PHARMACOLOGY/ULTRASTRUCTURE  Human  Immunohistochemistry
       Microscopy, Electron  Phosphatidylinositols/*METABOLISM  Phospholipase
       C/*METABOLISM  Support, Non-U.S. Gov't
       T-Lymphocytes/*METABOLISM/ULTRASTRUCTURE  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

