Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells.
Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells.
复制标题
DOI：
10.1172/jci118193
复制
发表时间：
1995-09
期刊：
影响因子：
--
通讯作者：
Xiao Xu;Shin-Heh Kang;O. Heidenreich;Michelle Okerholm;J. O’Shea;M. Nerenberg
中科院分区：
文献类型：
--
作者：
Xiao Xu;Shin-Heh Kang;O. Heidenreich;Michelle Okerholm;J. O’Shea;M. Nerenberg
HTLV-1感染会导致人类成人T细胞白血病。病毒编码的蛋白Tax被认为在肿瘤发生中起着重要作用。我们之前从TAX转基因小鼠模型中获得的数据显示，尽管TAX在两种组织中的表达水平相似，但TAX可以转化小鼠成纤维细胞，但不能转化胸腺细胞。在TAX转基因小鼠的胸腺细胞中，TRAX转基因小鼠的胸腺细胞中没有观察到130kD的S蛋白的结构性酪氨酸磷酸化。用磷酸化酪氨酸免疫沉淀和一组JAK激酶特异性抗体进行Western印迹分析，证实在TAX转化的小鼠成纤维细胞系中p130为JAK2，在HTLV-1转化的人T细胞系中为JAK3。TAX转化细胞中JAK2的磷酸化是IL-6高表达的结果。在Balb/c3T3细胞中，该蛋白的酪氨酸磷酸化也可以用来自B系的上清诱导，这与诱导细胞增殖有关。IL-6中和抗体可抑制细胞的磷酸化和增殖。在HTLV-1感染的人T细胞和转基因小鼠模型中，Jak激酶的结构性磷酸化可能促进肿瘤的生长。
HTLV-1 infection causes an adult T cell leukemia in humans. The viral encoded protein tax, is thought to play an important role in oncogenesis. Our previous data obtained from a tax transgenic mouse model revealed that tax transforms mouse fibroblasts but not thymocytes, despite comparable levels of tax expression in both tissues. Constitutive tyrosine phosphorylation of a 130-kD protein(s) was observed in the tax transformed fibroblast B line and in HTLV-1 transformed human lymphoid lines, but not in thymocytes from Thy-tax transgenic mice. Phosphotyrosine immunoprecipitation followed by Western blot analysis with a set of Jak kinase specific antibodies, identified p130 as Jak2 in the tax transformed mouse fibroblastic cell line and Jak3 in HTLV-1 transformed human T cell lines. Phosphorylation of Jak2 in tax transformed cells resulted from high expression of IL-6. Tyrosine phosphorylation of this protein could also be induced in Balb/c3T3 cells using a supernatant from the B line, which was associated with induction of cell proliferation. Both phosphorylation and proliferation were inhibited by IL-6 neutralizing antibodies. Constitutive phosphorylation of Jak kinases may facilitate tumor growth in both HTLV-1 infected human T cells and the transgenic mouse model.