This award will support collaborative research between Prof. John Burr of the University of Texas at Dallas and Prof. Paolo Comoglio of the University of Turin Medical School. The src gene of Rous sarcoma virus (RSV) is responsible for the ability of this virus to transform cells in culture and to induce tumors in birds and other animals. The investigators plan to determine the mechanism by which the protein encoded by the oncogene (src) of this virus results in a malignant transformation. With this in mind, they want to identify those cellular proteins that are natural substrates for the protein. They have obtained a library of monoclonal antibodies which are reactive against phosphotyrosine-containing proteins. Using these antibodies, they have begun to identify and purify individual candidate substrate proteins. The U.S. P.I.'s preliminary results on the purification and the generation of immunological reagents against the proteins discussed above are very encouraging. The Italian P.I. is one of the world leaders in the use of anti-phosphotyrosine antibodies and the researchers are experienced collaborators. The investigators are addressing an important problem with significant implications concerning our knowledge of cell transformations and malignancies.