Abstract
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 p60c-src, a cellular tyrosine kinase homologous to the oncogene product of Rous sarcoma virus2,3. Activation of p60c–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 p60c-src is subject to cell cycle-specific regulation. It is most active during mitosis and repressed in interphase11. Here we report that mitotic p60c-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, p60c-src(527F), where tyrosine 527 is substituted by phenylalanine, is also highly active in all phases of the cell cycle.
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Kaech, S., Covic, L., Wyss, A. et al. Association of p60c-src with polyoma virus middle-T antigen abrogating mitosis-specific activation. Nature 350, 431–433 (1991). https://doi.org/10.1038/350431a0
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DOI: https://doi.org/10.1038/350431a0
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