Association of p60^c-src with polyoma virus middle-T antigen abrogating mitosis-specific activation

POLYOMA middle-T antigen is required for tumorigenesis in animals and for viral transformation of a variety of cells in culture (reviewed in ref. 1). Middle-T associates with and thereby activates p60^c-src, a cellular tyrosine kinase homologous to the oncogene product of Rous sarcoma virus^2,3. Activation of p60^c-src by middle-T is accompanied both by dephosphorylation of tyrosine 527, a site which negatively regulates src kinase activity (reviewed in refs 4-6) and by autophosphorylation on tyrosine 416 (refs 7-10). Phosphoprotein p60^c-src is subject to cell cycle-specific regulation. It is most active during mitosis and repressed in interphase¹¹. Here we report that mitotic p60^c-src is dephosphorylated at tyrosine 527. We also show that in cells expressing middle-T, src kinase activity is high both in mitosis and during interphase. An oncogenic mutant src protein, p60^c-src(527F), where tyrosine 527 is substituted by phenylalanine, is also highly active in all phases of the cell cycle.