The biochemical basis of cellular transformation by the avian sarcoma viruses Rous sarcoma virus, Y73 virus and PRCII virus will be studied. Particular attention will be paid to the role of the phosphorylation of cellular proteins on tyrosine. The role of 1) the phosphorylation of the cytoskeletal protein vinculin and 2) the abundance of fibronectin in the determination of the morphology of transformed cells will be evaluated using viruses which induce atypical morphological transformation. The metabolism and the state of phosphorylation of the two cellular proteins, 80K and 50K, which are found bound to the transforming protein of Rous sarcoma virus will be studied in uninfected cells, in cells transformed by Rous sarcoma virus, and in cells transformed by other agents. Antisera specific to proteins which are substrates of tyrosine protein kinases will be prepared and used to identify cellular proteins which are regulated by the phosphorylation of tyrosine. finally, the state of phosphorylation and the activity of cellular tyrosine protein kinases in uninfected cells and in a variety of transformed cells will be determined. Immediate attention will be paid to the cellular homologue of the transforming protein of Rous sarcoma virus. Antisera useful for the study of the cellular homologues of the transforming proteins of Y73 virus and of PRCII virus will be developed. The structure and the mode of replication of the avian coronavirus infections bronchitis virus will be studied. The polypeptides present in the virion will be enumerated, compared in primary structure, and localized in the virion. The mRNA which is translated to yield each viral structural protein will be determined by in vitro translation of fractionated viral mRNAs. The post-translational processing of each protein will be studied by immunoprecipitation of the viral proteins from infected cells. Finally, the transcriptional mechanism which generates the family of subgenomic mRNAs will be characterized by UV target size analysis.

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National Cancer Institute (NCI)
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Virology Study Section (VR)
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Salk Institute for Biological Studies
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