The objectives of this proposal are two fold, one is to understand the nature and function of the transforming gene of avian sarcoma virus, v-onc, and its normal cellular counterpart, c-onc; the other is to elucidate the mechanism of the recombination between retroviral and cellular sequences in the process of the formation of sarcoma viruses. A newly characterized avian sarcoma virus, UR2, will be used as a model system to study the structure, sequence and function of v-onc and c-onc. The transforming gene of UR2, v-ros, and its cellular homologue, c-ros, will be analyzed by molecular cloning and sequencing. The sequence of v-ros will be compared with other v-onc genes coding for protein kinases to elucidate their structural and functional relationship. The sequence and transforming ability of c-ros and v-ros will be compared to see if there exists a fundamental difference that may differentiate the oncogenic potential of the two genes. The structure and level of expression of c-ros in various tissues of developing chickens will be studied to elucidate the role of c-ros in normal cells. The intracellular location and interaction of the v-ros product with cellular proteins, e.g. cytoskeletons, will be analyzed to pursue the process of transformation, in particular, to understand the basic for the unique transforming morphology of UR2 on chick cells. The mRNA of c-srs gene will be molecularly cloned to study its structure and potential transforming ability. The system of avian recovered sarcoma viruses (rASVs) that have been derived from src deletion mutants of Rous sarcoma virus will be used in the study of the mechanism of recombination between viral and cellular sequences. The viral sequence essential for the generation of rASVs will be defined. The sites of recombination and c-src sequences involved in the process will be located.
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