TRANSFORMING GENES OF AVIAN SARCOMA VIRUSES

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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.