       Document 0682
 DOCN  M9640682
 TI    HIV-induced apoptosis requires the CD4 receptor cytoplasmic tail and is
       accelerated by interaction of CD4 with p56lck.
 DT    9604
 AU    Corbeil J; Tremblay M; Richman DD; Department of Medicine, University of
       California, San Diego, La; Jolla 92093-0679, USA.
 SO    J Exp Med. 1996 Jan 1;183(1):39-48. Unique Identifier : AIDSLINE
       MED/96136746
 AB    The roles of the CD4 receptor and the src kinase p56lck were examined in
       the process of HIV-induced apoptosis of CD4+ T lymphocytes. The presence
       of the CD4 cytoplasmic tail was found to be essential in delivering an
       apoptotic signal, and interaction of CD4 with p56lck potentiated
       HIV-induced apoptosis. Apoptosis, but not HIV replication, was abrogated
       by deleting the NH2-terminal intracytoplasmic tail of CD4, or by
       mutating the two critical cysteines in this tail that are responsible
       for CD4-p56lck interaction. Introduction of p56lck in C8166-45 or MT-2
       cells, CD4+ T cell lines deficient for this protein, greatly increased
       HIV-induced apoptosis and syncytium formation. The ability of p56lck to
       deliver an apoptotic signal did not depend on its kinase function, since
       a kinase-deficient mutant was as effective as its normal counterpart in
       inducing apoptosis, suggesting that p56lck may act as an adapter to
       anchor other proteins to transduce the death signal.
 DE    src-Family Kinases/*METABOLISM  Antigens, CD4/GENETICS/*METABOLISM
       *Apoptosis  Base Sequence  Cell Fusion  Cell Transformation, Viral
       Cytopathogenic Effect, Viral  CD4-Positive
       T-Lymphocytes/*PATHOLOGY/VIROLOGY  Flow Cytometry  HIV-1/*GROWTH &
       DEVELOPMENT  Molecular Sequence Data  Peptide Fragments/METABOLISM
       Precipitin Tests  Protein Binding  *Signal Transduction  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, Non-P.H.S.  Support, U.S. Gov't,
       P.H.S.  JOURNAL ARTICLE

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

