Monden Y, Shindo-Okada N, Nishimura S
Banyu Tsukuba Research Institute.
Gan To Kagaku Ryoho. 1997 Sep;24(11):1563-70.
Azatyrosine is known to convert ras, raf or c-erbB-2-transformed NIH3T3 cells to a normal phenotype. We attempted to identify the signal-transduction process triggered by oncogenic c-ErbB-2 that was inhibited by azatyrosine. Azatyrosine did not suppress activation of Ras induced by introduction of c-ErbB-2. However, it inhibited increases in phosphorylation of c-Raf-1 induced by oncogenic c-ErbB-2. Furthermore, azatyrosine inhibited activation of the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element in response to stimulation by oncogenic c-ErbB-2. These results suggest that this agent acts downstream of Ras in signal transduction from oncogenic c-ErbB-2 to nuclear factors. Moreover, we found that azatyrosine was incorporated into proteins instead of tyrosine. The simultaneous presence of a high concentration of tyrosine inhibited the conversion to a normal phenotype of transformed cells by azatyrosine. These results strongly suggest that incorporation of azatyrosine into proteins might convert the transformed cells in to cells with a normal phenotype.
已知氮杂酪氨酸可将ras、raf或c-erbB-2转化的NIH3T3细胞转变为正常表型。我们试图确定由致癌性c-ErbB-2触发且被氮杂酪氨酸抑制的信号转导过程。氮杂酪氨酸并未抑制因导入c-ErbB-2而诱导的Ras激活。然而，它抑制了致癌性c-ErbB-2诱导的c-Raf-1磷酸化增加。此外，氮杂酪氨酸抑制了致癌性c-ErbB-2刺激下12-O-十四酰佛波醇-13-乙酸酯（TPA）反应元件的激活。这些结果表明，该试剂在从致癌性c-ErbB-2到核因子的信号转导中作用于Ras的下游。此外，我们发现氮杂酪氨酸取代酪氨酸掺入蛋白质中。高浓度酪氨酸的同时存在抑制了氮杂酪氨酸将转化细胞转变为正常表型。这些结果强烈表明，氮杂酪氨酸掺入蛋白质可能将转化细胞转变为具有正常表型的细胞。
