Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri.
A protein, called tip, of herpesvirus saimiri associates with Lck in transformed T cells. To investigate the effects of complex formation on cellular signal transduction, we constructed human Jurkat-T-cell lines expressing tip. The expression of tip in Jurkat-T cells dramatically suppressed cellular tyrosine phosphorylation and surface expression of lymphocyte antigens. The expression of tip also blocked the induction of tyrosine phosphorylation by anti-CD3 stimulation. The expression of tip in fibroblast cells suppressed the transforming activity of oncogenic F505 Lck. Binding assays showed that the SH3 domain of Lck is sufficient to form a stable complex with tip in vitro. These results demonstrate that tip acts at an early stage of the T-cell signal transduction cascade by associating with Lck and downregulating Lck-mediated activation. Inhibition of Lck-mediated signal transduction by tip in T cells appears to be analogous to the inhibition of Lyn/Syk-mediated signal transduction in B cells by LMP2A of the B-cell-tropic Epstein-Barr virus.
D001483:Base Sequence; D002460:Cell Line; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D008970:Molecular Weight; D010750:Phosphoproteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology / Q000821:virology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D019061:src-Family Kinases / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*
D017931:DNA Primers; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C092384:tyrosine kinase interacting protein, Saimiriine herpesvirus 2; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases