TRANSFORMING GENES OF AVIAN SARCOMA VIRUSES

这项研究的目的是阐明细胞凋亡的机制。 癌基因ROS转化 禽类携带的v-ros癌基因 肉瘤病毒UR 2编码受体样蛋白酪氨酸激酶 (PTK)在其PTK结构域中与胰岛素的那些具有密切的同源性 和胰岛素样生长因子I受体。 本研究的重点 将对识别的属性和蜂窝 对细胞转化和信号传导重要的底物 V-ROS和C-ROS蛋白的过程。 此外，蛋白质的影响 酪氨酸磷酸酶（PTPases）在ros-mediated细胞 还将研究转型。 这些问题将 利用鸡和哺乳动物中特定的ros突变体进行研究 细胞转化以及特异于 ROS蛋白的单个底物。 具体目标是： 1.调控其激酶活性的ros序列的鉴定， 底物相互作用和转化能力。 2.分离对以下底物特异的单克隆抗体 罗斯 3.生物化学性质的鉴定，特别是 对ROS转化细胞重要的底物。 4.表达和信号传导功能的表征 原癌基因c-ros 5. PTPases对细胞转化和信号转导作用的研究 ROS的功能 希望本研究能进一步加深我们对 这种受体样PTK癌基因的细胞转化机制。

The goal of the proposed study is to elucidate the mechanisms of cell transformation by oncogene ros. The v-ros oncogene carried by avian sarcoma virus UR2 codes for a receptor-like protein tyrosine kinase (PTK) bearing close homology in its PTK domain with those of insulin and insulin-like growth factor I receptors. The focus of this study will be on the identification of the properties and cellular substrates important for the cell transforming and signalling processes of v- and c-ros proteins. In addition, effect of protein tyrosine phosphatases (PTPases) on the ros-mediated cell transformation will also be investigated. These problems will be approached by using specific ros mutants in chicken and mammalian cell transformation as well as monoclonal antibodies specific to individual substrates of the ros protein. The Specific Aims are: 1. Identification of ros sequences modulating its kinase activity, substrate interaction and transforming ability. 2. Isolation of monoclonal antibodies specific for the substrates of ros. 3. Identification of biochemical properties, especially the substrate(s) important for cell transformation by ros. 4. Characterization of the expression and signal transducing function of protooncogene c-ros. 5. Study of the effect of PTPases on cell transforming and signalling function of ros. It is hoped that this study will further our understanding of the mechanism of cell transformation by this receptor-like PTK oncogene.