The transformation of cells by the retrovirus, Rous sarcoma virus (RSV), is attributed to the cellular function of a 60 kilodalton protein product of the viral src gene, pp60?v-src?. This 60 kilodalton protein is a protein kinase, specifically phosphorylating tyrosine residue. It is generally appreciated that pp60?v-src? may have several cellular targets whose physiological functions are affected by phosphorylation of one or more tyrosine residues. These individual enzyme-substrate interactions could account for the changes in cells as they undergo transformation, i.e., rounded morphology, anchorage-independent growth, loss of density-dependent inhibition of division, increased ion and glucose transport, production of proteases (i.e., plasminogen activator), and loss of cell surface fibronectin. Infection with partially defective mutants of RSV may result in the selective appearance of one or more of these cellular phenotypes. For the most part, these partially defective mutants have been prepared by a random mutagenic procedure. We now are applying recently developed procedures that will allow mutagenesis in defined areas of pp60?v-src? and ultimately, specific to certain amino acids. By this procedure we hope to define the composition of the active site of the enzyme and the corresponding binding sites to putative individual proteins that result in the pleiotypic changes in the transformation process. (X)
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