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 language | English (US) |
|---|---|
| Pages (from-to) | 7814-7822 |
| Number of pages | 9 |
| Journal | Journal of Virology |
| Volume | 69 |
| Issue number | 12 |
| State | Published - 1995 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri
AU - Jung, J. U.
AU - Lang, S. M.
AU - Jun, T.
AU - Roberts, T. M.
AU - Veillette, A.
AU - Desrosiers, Ronald Charles
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0028800298&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028800298&partnerID=8YFLogxK
M3 - Article
C2 - 7494293
AN - SCOPUS:0028800298
VL - 69
SP - 7814
EP - 7822
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 12
ER -