THE TRANSFORMING GENES OF AVIAN RNA TUMOR VIRUSES

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The purpose of the proposed research is to elucidate the function(s) of the oncogene v-ros present in avian sarcoma virus UR2 described by us. We have recently discovered that the oncogene products p68ros of avian sarcoma virus UR2 is associated with a phosphatidyl inositol (PtdIns) kinase activity in vitro, and the UR2 transformed cells show enhanced polyphosphoinositide turnover. It is possible that ptdIns phosphorylation might contribute to malignant transformation of susceptible cells by generating abnormally high levels of 1,2-diacylglycerol, which appears to be the endogeneous activator of the phorbol ester receptor (kinase C). similar observations have been made on ppSrc by Sugimoto et al. We intend to investigate whether the kinase activity associated with p68ros is an intrinsic property of the protein or whether this protein has a regulatory role in the phosphorylation of phosphoinositols. We plan to answer this question by introducing the molecularly cloned genome of UR2 in expression vectors and obtain expression of p68ros in prokaryotic cells. We also propose to continue our genetic studies of UR2 AV and carry out a genetic analysis of the ros gene in an attempt to correlate specific lesions, small deletions, and point mutations in the ros sequence, with specific phenotypes of the transformed cells. The goal of this investigation is to obtain a physical-genetic map of this oncogene. We finally plan to investigate the interaction of avian vital oncogene expression and development of differentiation markers in neuroretinal cells in an attempt to shed light on the normal function of the corresponding proto-oncogenes.