Whitman M, Kaplan D R, Schaffhausen B, Cantley L, Roberts T M
Nature. 1985;315(6016):239-42. doi: 10.1038/315239a0.
Polyoma middle-T antigen is required for viral transformation of cultured cells and for tumorigenesis in animals. Like many other transforming gene products, middle-T is bound to the membrane and has an associated tyrosine kinase activity in vitro. This activity seems to result from the interaction of middle-T with pp60c-src, the cellular homologue of the transforming gene product of the Rous sarcoma virus, pp60v-src (refs 3-5). Both pp60v-src (ref. 6) and another retrovirus transforming gene product, pp68v-ros (ref. 7) were shown recently to have an associated phosphatidylinositol (PI) kinase activity in vitro and to increase PI turnover in vivo. These results suggest that viral transformation may be directly connected to a complex network of second messengers generated from PI turnover. Here, we assayed for PI kinase activity in immunoprecipitates made with middle-T- or pp60c-src-specific antisera of cells infected with polyoma virus. A PI kinase activity was detected in those immunoprecipitates which contained middle-T. Studies of mutants of middle-T defective in transformation indicate a close correlation between PI kinase activity and transformation.
多瘤病毒中T抗原对于培养细胞的病毒转化以及动物体内的肿瘤发生是必需的。与许多其他转化基因产物一样，中T与细胞膜结合，并且在体外具有相关的酪氨酸激酶活性。这种活性似乎是由于中T与pp60c-src相互作用的结果，pp60c-src是劳氏肉瘤病毒转化基因产物pp60v-src的细胞同源物（参考文献3 - 5）。最近研究表明，pp60v-src（参考文献6）和另一种逆转录病毒转化基因产物pp68v-ros（参考文献7）在体外均具有相关的磷脂酰肌醇（PI）激酶活性，并且在体内可增加PI周转。这些结果表明，病毒转化可能直接与由PI周转产生的复杂第二信使网络相关。在此，我们用多瘤病毒感染细胞的中T或pp60c-src特异性抗血清制备的免疫沉淀物中检测PI激酶活性。在那些含有中T的免疫沉淀物中检测到了PI激酶活性。对转化缺陷的中T突变体的研究表明PI激酶活性与转化之间存在密切相关性。
