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

J. U. Jung, S. M. Lang, T. Jun, T. M. Roberts, A. Veillette, Ronald Charles Desrosiers

Research output: Contribution to journalArticle

75 Citations (Scopus)

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
StatePublished - 1995
Externally publishedYes

Fingerprint

Saimiriine herpesvirus 2
Saimiriine Herpesvirus 2
signal transduction
Signal Transduction
Down-Regulation
T-lymphocytes
T-Lymphocytes
Jurkat Cells
B-lymphocytes
Tyrosine
tyrosine
phosphorylation
B-Lymphocytes
Phosphorylation
lymphocyte antigens
Human herpesvirus 4
src Homology Domains
Human Herpesvirus 4
fibroblasts
tropics

ASJC Scopus subject areas

  • Immunology

Cite this

Jung, J. U., Lang, S. M., Jun, T., Roberts, T. M., Veillette, A., & Desrosiers, R. C. (1995). Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri. Journal of Virology, 69(12), 7814-7822.

Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri. / Jung, J. U.; Lang, S. M.; Jun, T.; Roberts, T. M.; Veillette, A.; Desrosiers, Ronald Charles.

In: Journal of Virology, Vol. 69, No. 12, 1995, p. 7814-7822.

Research output: Contribution to journalArticle

Jung, JU, Lang, SM, Jun, T, Roberts, TM, Veillette, A & Desrosiers, RC 1995, 'Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri', Journal of Virology, vol. 69, no. 12, pp. 7814-7822.
Jung JU, Lang SM, Jun T, Roberts TM, Veillette A, Desrosiers RC. Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri. Journal of Virology. 1995;69(12):7814-7822.
Jung, J. U. ; Lang, S. M. ; Jun, T. ; Roberts, T. M. ; Veillette, A. ; Desrosiers, Ronald Charles. / Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri. In: Journal of Virology. 1995 ; Vol. 69, No. 12. pp. 7814-7822.
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