Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri

Jae U. Jung, Sabine M. Lang, Toni Jun, Thomas M. Roberts, André Veillette, Ronald C. Desrosiers

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7814-7822
Number of pages9
JournalJournal of virology
Volume69
Issue number12
DOIs
StatePublished - Dec 1995

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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