DOWN-REGULATION OF LCK-MEDIATED SIGNAL-TRANSDUCTION BY TIP OF HERPESVIRUS SAIMIRI

被引:72
作者
JUNG, JU
LANG, SM
JUN, T
ROBERTS, TM
VEILLETTE, A
DESROSIERS, RC
机构
[1] HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT CELLULAR & MOLEC BIOL,BOSTON,MA 02115
[2] MCGILL UNIV,MCGILL CANC CTR,MONTREAL,PQ H3G 1Y6,CANADA
[3] MCGILL UNIV,DEPT BIOCHEM,MONTREAL,PQ H3G 1Y6,CANADA
关键词
D O I
10.1128/JVI.69.12.7814-7822.1995
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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,vith 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.
引用
收藏
页码:7814 / 7822
页数:9
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