Xu X, Kang S H, Heidenreich O, Okerholm M, O'Shea J J, Nerenberg M I
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA.
J Clin Invest. 1995 Sep;96(3):1548-55. doi: 10.1172/JCI118193.
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.
人类嗜T淋巴细胞病毒1型（HTLV-1）感染可导致人类患成人T细胞白血病。病毒编码的蛋白Tax被认为在肿瘤发生过程中起重要作用。我们先前从Tax转基因小鼠模型获得的数据显示，尽管Tax在两种组织中的表达水平相当，但Tax可使小鼠成纤维细胞发生转化，却不能使胸腺细胞发生转化。在Tax转化的成纤维细胞B系和HTLV-1转化的人淋巴系中观察到一种130-kD蛋白的组成型酪氨酸磷酸化，但在Thy-tax转基因小鼠的胸腺细胞中未观察到。用一组Jak激酶特异性抗体进行磷酸酪氨酸免疫沉淀后再进行蛋白质印迹分析，在Tax转化的小鼠成纤维细胞系中鉴定出p130为Jak2，在HTLV-1转化的人T细胞系中鉴定出p130为Jak3。Tax转化细胞中Jak2的磷酸化是由IL-6的高表达引起的。使用B系的上清液也可在Balb/c3T3细胞中诱导该蛋白的酪氨酸磷酸化，这与细胞增殖的诱导有关。磷酸化和增殖均被IL-6中和抗体抑制。Jak激酶的组成型磷酸化可能在HTLV-1感染的人T细胞和转基因小鼠模型中均促进肿瘤生长。
