Lee E B, Beug H, Hayman M J
Department of Microbiology, State University of New York, Stony Brook 11794.
Oncogene. 1993 May;8(5):1317-27.
The v-erbB protein encoded by the avian erythroblastosis virus AEV-H is responsible for the transformation of fibroblasts and erythroblasts by this virus. Deletion of amino acids 961-1102, which lie carboxy terminal to the kinase domain of the v-erbB protein, destroys the ability of the virus to transform erythroid cells without severely affecting fibroblast transformation. This region is termed the E-domain and has been postulated to contain a region important for erythroid cell transformation. In-frame deletions of approximately 23 amino acids were introduced throughout the E-domain in an attempt to locate a specific region that was essential for erythroid cell transformation. Several of the deletions gave rise to a partial transformed phenotype, although no single deletion that completely abolished erythroid cell transformation was found. Interestingly, deletion of amino acids 1031-1055 resulted in a superactivated v-erbB protein that was more active for erythroid cell transformation than the wild-type AEV-H v-erbB protein. This indicates that there is a negative regulatory region located within this region that normally partially suppresses the transforming activity of the v-erbB protein for erythroid cells. These data suggest that the E-domain contains both negative and positive regulatory regions that function in erythroid cells, and complete deletion of the region is necessary to abolish erythroid cell transformation.
禽成红细胞增多症病毒AEV-H编码的v-erbB蛋白负责该病毒对成纤维细胞和红细胞的转化。v-erbB蛋白激酶结构域羧基末端的氨基酸961-1102缺失，会破坏病毒转化红细胞的能力，但不会严重影响成纤维细胞的转化。该区域被称为E结构域，据推测含有对红细胞转化重要的区域。为了定位对红细胞转化至关重要的特定区域，在整个E结构域引入了约23个氨基酸的读框内缺失。尽管未发现完全消除红细胞转化的单一缺失，但有几个缺失产生了部分转化表型。有趣的是，氨基酸1031-1055的缺失产生了一种超活化的v-erbB蛋白，其对红细胞转化的活性比野生型AEV-H v-erbB蛋白更高。这表明该区域内存在一个负调控区域，该区域通常会部分抑制v-erbB蛋白对红细胞的转化活性。这些数据表明，E结构域包含在红细胞中起作用的负调控和正调控区域，完全删除该区域对于消除红细胞转化是必要的。
