Association of p60c-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 p60c-src, a cellular tyrosine kinase homologous to the oncogene product of Rous sarcoma virus. Activation of p60c-src by middle-T is accompanied both by dephosphorylation of tyrosine 527, a site which negatively regulates src kinase 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 interphase. 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.
Kaech
S
S
Friedrich Miescher-Institute, Basel, Switzerland.
Covic
L
L
Wyss
A
A
Ballmer-Hofer
K
K
D000818:Animals; D000911:Antibodies, Monoclonal; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002478:Cells, Cultured; D051379:Mice; D008938:Mitosis; D009154:Mutation; D010449:Peptide Mapping; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000952:Antigens, Polyomavirus Transforming; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src)