Courtneidge S A
Cancer Surv. 1986;5(2):173-82.
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.
多瘤病毒的转化蛋白，即中T抗原，是一种与膜相关的磷蛋白。中T与细胞酪氨酸激酶pp60c-src形成复合物，并被其磷酸化。突变分析表明，这种复合物的形成对多瘤病毒的转化至关重要。中T的结合导致pp60c-src在其氨基末端的新位点进行自身磷酸化，并增加了该酶的比活性。然而，中T的至少一种非转化突变体dl1015也能以这些方式激活pp60c-src。这表明，除了激活pp60c-src的能力外，中T的其他特性对于转化也是必需的。这些特性可能包括与磷脂酰肌醇激酶和/或与61 kDa蛋白质结合的能力。中T激活pp60c-src的机制可能涉及其改变该酶磷酸化状态的能力，从而在体内干扰pp60c-src活性的调节。多瘤病毒转化细胞可能是研究pp60c-src活性控制以及确定该酶底物的良好模型系统。
