Polyoma virus transforming protein associates with the product of the c-src cellular gene

Polyoma virus can transform the growth properties of rodent cells grown in culture and form tumours in susceptible animals, an activity largely due to one of the virus-encoded proteins, called middle T. Middle T has an associated tyrosine-specific protein kinase activity in vitro and interacts with cellular membranes, but the biochemical basis of its ability to transform remains unclear. Although there is some correlation between the transforming activity of different polyoma virus mutants and their ability to accept phosphate on tyrosine in middle T in the in vitro kinase reaction, the abundance of phosphotyrosine in protein is not elevated in polyoma virus-transformed cells and no cellular substrates for the putative kinase have been identified. It is also not yet known whether the tyrosine kinase of middle T is an intrinsic activity of the protein itself or the property of an associated enzyme. The experiments described here indicate that a fraction of middle T forms a stable complex with pp60c-src, the product of a cellular oncogene, and lead us to propose that the middle T associated kinase at least in part is a property of pp60c-src rather than middle T itself.