Biesinger B, Tsygankov A Y, Fickenscher H, Emmrich F, Fleckenstein B, Bolen J B, Bröker B M
Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, Federal Republic of Germany.
J Biol Chem. 1995 Mar 3;270(9):4729-34. doi: 10.1074/jbc.270.9.4729.
Subgroup C strains of Herpesvirus saimiri, a leukemogenic virus of non-human primates, transform human T cells to permanent growth in culture. These cell retain their antigen specificity, and they are becoming widely used as a model for activated human T cells. Though a variety of human cell types can be infected by H. saimiri, transformation appears to be specific for CD4+ and CD8+ T cells. Our investigation of early signaling events in H. saimiri-transformed T cells revealed a novel 40-kDa phosphoprotein complexed with the T cell-specific tyrosine protein kinase p56lck. This protein, termed Tip (tyrosine kinase interacting protein), is identified as a viral protein encoded by the open reading frame 1 (ORF1). In the transformed cells Tip is expressed together with the gene product of ORF2, the viral oncoprotein StpC, which acts on epithelial cells. The H. saimiri genome has 75 ORFs, but only ORF1 and ORF2 are transcribed in transformed human cells. Tip is phosphorylated on tyrosine in cell-free systems containing Lck, indicating that the viral protein is a substrate for this T cell-specific kinase. Alteration of T cell signaling pathways by Tip may be the second event complementing the action of StpC in a new mechanism of T cell transformation.
猴疱疹病毒C亚群毒株是一种非人类灵长类动物的致白血病病毒，可将人类T细胞转化为在培养中能永久生长的细胞。这些细胞保留了它们的抗原特异性，并且正被广泛用作活化人类T细胞的模型。虽然多种人类细胞类型可被猴疱疹病毒感染，但转化似乎对CD4⁺和CD8⁺ T细胞具有特异性。我们对猴疱疹病毒转化的T细胞中早期信号事件的研究揭示了一种与T细胞特异性酪氨酸蛋白激酶p56lck复合的新型40 kDa磷蛋白。这种蛋白被称为Tip（酪氨酸激酶相互作用蛋白），被鉴定为开放阅读框1（ORF1）编码的病毒蛋白。在转化细胞中，Tip与ORF2的基因产物、作用于上皮细胞的病毒癌蛋白StpC一起表达。猴疱疹病毒基因组有75个开放阅读框，但在转化的人类细胞中只有ORF1和ORF2被转录。在含有Lck的无细胞系统中，Tip在酪氨酸上被磷酸化，这表明该病毒蛋白是这种T细胞特异性激酶的底物。Tip对T细胞信号通路的改变可能是在T细胞转化的新机制中补充StpC作用的第二个事件。
