Summers S A, Lipfert L, Birnbaum M J
Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Biochem Biophys Res Commun. 1998 May 8;246(1):76-81. doi: 10.1006/bbrc.1998.8575.
Polyoma middle T antigen (PMT) was originally identified as the tumorigenic component of the polyomavirus genome. To investigate whether the serine/ threonine kinase Akt/PKB, which is the proto-oncogene transduced by the transforming AKT8 retrovirus, is activated by PMT, 3T3-L1 fibroblasts were stably transfected with wild type PMT. PMT expression accelerated glucose transport and increased phosphorylation of p70 S6-kinase and MAPK. PMT expression also stimulated Akt kinase activity 7 fold as compared to untreated, mock infected cells. This stimulation rivaled that obtained following insulin treatment of both mock and PMT infected cells. Akt activation and phosphorylation were eliminated in a PMT mutant incapable of interacting with PI3-kinase, but not one which does not interact with Shc, and correlated closely to the amount of PI3-kinase activity in anti-phosphotyrosine immunoprecipitates. These results indicate that the PI3-kinase pathway is requisite, but the Shc pathway is dispensable, for Akt activation. The studies further suggest that Akt may participate in PMT and PI3-kinase's regulation of cellular transformation and tumorigenesis.
多瘤病毒中T抗原（PMT）最初被鉴定为多瘤病毒基因组的致瘤成分。为了研究由转化型AKT8逆转录病毒转导的原癌基因丝氨酸/苏氨酸激酶Akt/PKB是否被PMT激活，用野生型PMT稳定转染3T3-L1成纤维细胞。与未处理的、模拟感染的细胞相比，PMT表达加速了葡萄糖转运，并增加了p70 S6激酶和丝裂原活化蛋白激酶（MAPK）的磷酸化。PMT表达还使Akt激酶活性提高了7倍。这种刺激与胰岛素处理模拟感染和PMT感染细胞后获得的刺激相当。在一个无法与PI3激酶相互作用的PMT突变体中，Akt的激活和磷酸化被消除，但在一个不与Shc相互作用的突变体中则没有，并且与抗磷酸酪氨酸免疫沉淀物中PI3激酶活性的量密切相关。这些结果表明，PI3激酶途径对于Akt激活是必需的，但Shc途径是可有可无的。这些研究进一步表明，Akt可能参与PMT和PI3激酶对细胞转化和肿瘤发生的调节。
