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 animals¹, an activity largely due^1-3 to one of the virus-encoded proteins, called middle T. Middle T has an associated tyrosine-specific protein kinase activity in vitro ^4-6 and interacts with cellular membranes⁷, 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 reaction⁴, the abundance of phos-photyrosine in protein is not elevated in polyoma virus-transformed cells⁸ 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 pp60^c-src, the product of a cellular oncogene⁹, and lead us to propose that the middle T associated kinase at least in part is a property of pp60^c-src rather than middle T itself.