Transformation by polyoma virus middle T antigen.
The transforming protein of polyoma virus, middle T antigen, is a membrane-associated phosphoprotein. Middle T forms a complex with, and is phosphorylated by, a cellular tyrosine kinase pp60c-src. Mutant analysis suggests that formation of this complex is critical to transformation by polyoma. Middle T binding causes pp60c-src to autophosphorylate at novel sites in its amino terminus, and increases the specific activity of the enzyme. However, at least one non-transforming mutant of middle T, dl1015, can also activate pp60c-src in these ways. This suggests that properties of middle T other than the ability to activate pp60c-src are also necessary for transformation. These properties may include the ability to associate with a phosphatidylinositol kinase, and/or with a protein of 61 kDa. The mechanism by which middle T activates pp60c-src may involve its ability to alter the phosphorylation state of the enzyme, and thus interfere with the regulation of pp60c-src activity in vivo. Polyoma virus transformed cells might then be a good model system for investigating the control of pp60c-src activity as well as defining substrates of the enzyme.
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D005814:Genes, Viral; D051379:Mice; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D009857:Oncogenes; D010770:Phosphotransferases / Q000235:genetics; D011120:Polyomavirus / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016392:Proto-Oncogene Proteins pp60(c-src)
D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D010770:Phosphotransferases; D011494:Protein Kinases; D019870:1-Phosphatidylinositol 4-Kinase; D016392:Proto-Oncogene Proteins pp60(c-src)