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1996-02-26
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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).