Insulin-like growth factor I receptor signaling and nuclear translocation of insulin receptor substrates 1 and 2.
Insulin-like growth factor I receptor signaling and nuclear translocation of insulin receptor substrates 1 and 2.
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DOI：
10.1210/me.2002-0276
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发表时间：
2003-03
影响因子：
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通讯作者：
Hongzhi Sun;X. Tu;M. Prisco;A. Wu;Ivan Casiburi;R. Baserga
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文献类型：
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作者：
Hongzhi Sun;X. Tu;M. Prisco;A. Wu;Ivan Casiburi;R. Baserga
胰岛素受体底物1(IRS-1)可以转位到几种类型的细胞的核和核仁中。激活的胰岛素样生长因子1受体(IGF-IR)和某些癌基因(如猿猴病毒40T抗原和v-src)可以诱导核转位。我们问过IRS-2是否也可以移位到原子核。此外，我们还研究了IGF-IR功能突变对IRS蛋白核转位的影响。IRS-2转位到表达IGF-IR的小鼠胚胎成纤维细胞的细胞核，但与IRS-1不同，不转位到表达猿猴病毒40T抗原的细胞中。IGF-IR酪氨酸激酶域的突变消除了IRS蛋白的易位。IGF-IR的其他突变不会干扰其有丝分裂能力，但会抑制其转化能力，导致易位减少，特别是对核仁的易位。核IRS-1和IRS-2与上游结合因子相互作用，上游结合因子是RNA聚合酶I活性的关键调节因子，因此，rRNA合成。在野生型而不是突变型的32D细胞中，IRS-1导致核糖体DNA启动子的显著激活。核IRS蛋白与上游结合因子1的相互作用构成了这些蛋白与核糖体DNA转录机制的第一个直接联系。
The insulin receptor substrate 1 (IRS-1) can translocate to the nuclei and nucleoli of several types of cells. Nuclear translocation can be induced by an activated insulin-like growth factor 1 receptor (IGF-IR), and by certain oncogenes, such as the Simian virus 40 T antigen and v-src. We have asked whether IRS-2 could also translocate to the nuclei. In addition, we have studied the effects of functional mutations in the IGF-IR on nuclear translocation of IRS proteins. IRS-2 translocates to the nuclei of mouse embryo fibroblasts expressing the IGF-IR, but, at variance with IRS-1, does not translocate in cells expressing the Simian virus 40 T antigen. Mutations in the tyrosine kinase domain of the IGF-IR abrogate translocation of the IRS proteins. Other mutations in the IGF-IR, which do not interfere with its mitogenicity but inhibit its transforming capacity, result in a decrease in translocation, especially to the nucleoli. Nuclear IRS-1 and IRS-2 interact with the upstream binding factor, which is a key regulator of RNA polymerase I activity and, therefore, rRNA synthesis. In 32D cells, wild-type, but not mutant, IRS-1 causes a significant activation of the ribosomal DNA promoter. The interaction of nuclear IRS proteins with upstream binding factor 1 constitutes the first direct link of these proteins with the ribosomal DNA transcription machinery.