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首页> 外文期刊>Molecular and Cellular Biology >Association of insulin receptor substrate 1 with simian virus 40 large T antigen.
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Association of insulin receptor substrate 1 with simian virus 40 large T antigen.

机译：胰岛素受体底物1与猿猴病毒40大T抗原的关联。

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Mouse embryo cells expressing a wild-type number of insulin-like growth factor I receptors (IGF-IR) (W cells) can be transformed either by simian virus 40 large T antigen (SV40 T) or by overexpressed insulin receptor substrate 1 (IRS-1), singly transfected. Neither SV40 T antigen nor IRS-1, individually, can transform mouse embryo cells with a targeted disruption of the IGF-IR genes (R- cells). However, cotransfection of SV40 T antigen and IRS-1 does transform R- cells. In this study, using different antibodies and different cell lines, we found that SV40 T antigen and IRS-1 are coprecipitated from cell lysates in a specific fashion, regardless of whether the lysates are immunoprecipitated with an antibody to SV40 T antigen or an antibody to IRS-1. The same antibody to SV40 T antigen, however, fails to coprecipitate another substrate of IGF-IR, the transforming protein Shc, and two other signal-transducing molecules, Grb2 and Sos. Finally, an SV40 T antigen lacking the amino-terminal 250 amino acids fails to coprecipitate IRS-1 and also fails to transform R- cells overexpressing mouse IRS-1. These experiments indicate that IRS-1 associates with SV40 T antigen and that this association plays a critical role in the combined ability of these proteins to transform R- cells. This finding is discussed in light of the crucial role of the IGF-IR in the establishment and maintenance of the transformed phenotype.
机译：可以通过猿猴病毒40大T抗原（SV40 T）或过表达的胰岛素受体底物1（IRS）转化表达野生型数量的胰岛素样生长因子I受体（IGF-IR）的小鼠胚胎细胞（W细胞） -1），单独转染。 SV40 T抗原和IRS-1都不能单独转化具有IGF-IR基因（R-细胞）靶向破坏的小鼠胚胎细胞。但是，SV40 T抗原和IRS-1的共转染确实可以转化R细胞。在这项研究中，使用不同的抗体和不同的细胞系，我们发现SV40 T抗原和IRS-1以特定的方式从细胞裂解物中共沉淀，无论裂解物是用针对SV40 T抗原的抗体还是针对SV40 T抗原的抗体免疫沉淀的IRS-1。但是，针对SV40 T抗原的同一抗体无法共沉淀IGF-IR的另一种底物，转化蛋白Shc和另外两种信号转导分子Grb2和Sos。最后，缺少氨基末端250个氨基酸的SV40 T抗原不能共沉淀IRS-1，也不能转化过表达小鼠IRS-1的R细胞。这些实验表明IRS-1与SV40 T抗原缔合，并且这种缔合在这些蛋白质转化R细胞的综合能力中起着关键作用。根据IGF-1R在建立和维持转化表型中的关键作用讨论了这一发现。

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