Insulin-Like Growth Factor I Receptor Signaling and Nuclear Translocation of Insulin Receptor Substrates 1 and 2
| Autor: | Hongzhi Sun, Ivan Casiburi, Renato Baserga, Marco Prisco, Xiao Tu, An Wu |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Nucleolus
medicine.medical_treatment Blotting Western Active Transport Cell Nucleus Chromosomal translocation Receptor IGF Type 1 Mice Endocrinology medicine Animals Phosphorylation Receptor Molecular Biology Cell Nucleus Microscopy Confocal biology Growth factor Intracellular Signaling Peptides and Proteins 3T3 Cells General Medicine Phosphoproteins Immunohistochemistry Molecular biology IRS1 Insulin receptor Cell nucleus medicine.anatomical_structure RNA Ribosomal Mutation Insulin Receptor Substrate Proteins biology.protein Pol1 Transcription Initiation Complex Proteins Tyrosine kinase Signal Transduction Subcellular Fractions |
| Zdroj: | Molecular Endocrinology. 17:472-486 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|