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. 1995 Dec;69(12):7814–7822. doi: 10.1128/jvi.69.12.7814-7822.1995

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

J U Jung 1, S M Lang 1, T Jun 1, T M Roberts 1, A Veillette 1, R C Desrosiers 1
PMCID: PMC189725  PMID: 7494293

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.

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Selected References

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