title: HIV-induced apoptosis requires the CD4 receptor cytoplasmic tail and is accelerated by interaction of CD4 with p56lck.
abstract: 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.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla 92093-0679, USA.
authors.forename: J
authors.initials: J
authors.lastname: Corbeil
authors.forename: M
authors.initials: M
authors.lastname: Tremblay
authors.forename: D D
authors.initials: DD
authors.lastname: Richman
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology* / Q000821:virology; D002459:Cell Fusion; D002472:Cell Transformation, Viral; D003588:Cytopathogenic Effect, Viral; D005434:Flow Cytometry; D015497:HIV-1 / Q000254:growth & development*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D010446:Peptide Fragments; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases