TRANSFORMING GENES OF AVIAN SARCOMA VIRUSES

这项拟议研究的目标是阐明细胞的机制 癌基因ros转化。禽类携带的v-ros癌基因 肉瘤病毒UR2编码一种受体样蛋白酪氨酸激酶 (PTK)的PTK结构域与胰岛素的PTK结构域具有密切的同源性 和胰岛素样生长因子I受体。这项研究的重点是 将对财产和蜂窝进行鉴定 细胞转化和信号传递的重要底物 V-ros和c-ros蛋白的研究进展。此外，蛋白质的影响 ROS介导的细胞上的酪氨酸磷酸酶(PTPase) 还将对转型进行调查。这些问题将是 利用鸡和哺乳动物中特定的ros突变体进行探讨 细胞转化以及特异性的单抗 Ros蛋白的单个底物。 具体目标是： 1.鉴定调节ITS激酶活性的ROS序列， 底物相互作用和转化能力。 2.针对底物的单抗的分离 罗斯。 3.生化特性的鉴定，特别是 底物(S)在ros转化细胞中起重要作用。 4.表达和信号转导功能的表征 原癌基因c-ros。 5.PTPase在细胞转化和信号转导中的作用 ROS的功能。 希望这项研究将进一步加深我们对 该受体样癌基因PTK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.