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Journal article
Insulin-like Growth Factor I-mediated Degradation of Insulin Receptor Substrate-1 Is Inhibited by Epidermal Growth Factor in Prostate Epithelial Cells
The Journal of biological chemistry, v 275(29), pp 22558-22562
21 Jul 2000
PMID: 10811632
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We have sought to determine whether insulin-like growth factor I (IGF-I) regulates the levels of insulin receptor substrate-1 (IRS-1) in prostate epithelial cells. Exposure of prostate epithelial cells to IGF-I in the absence of other growth factors leads to a reduction in IRS-1 levels. Ubiquitin content of IRS-1 is increased in the presence of IGF-I, and inhibitors of the proteasome prevented the reduction of IRS-1 levels seen following IGF-I exposure. These results imply that IRS-1 is targeted to the proteasome upon exposure to IGF-I. The addition of epidermal growth factor (EGF) maintained IRS-1 levels even in the presence of IGF-I and inhibits IGF-I-dependent ubiquitination of IRS-1. Thus, these two growth factors, IGF-I and EGF, had antagonistic effects on IRS-1 protein levels in prostate epithelial cells. This regulation of IRS-1 reveals a novel level of cross-talk between the IGF-I and EGF signal pathways, which may have implications in tumors that harbor activating mutations in the EGF receptor.
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Details
- Title
- Insulin-like Growth Factor I-mediated Degradation of Insulin Receptor Substrate-1 Is Inhibited by Epidermal Growth Factor in Prostate Epithelial Cells
- Creators
- Hong Zhang - Drexel UniversityHenry Hoff - Lankenau Medical CenterChristian Sell - Thomas Jefferson UniversityHua Zhang - Electrical and Computer Engineering
- Publication Details
- The Journal of biological chemistry, v 275(29), pp 22558-22562
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Electrical and Computer Engineering
- Web of Science ID
- WOS:000088363800108
- Scopus ID
- 2-s2.0-0034698105
- Other Identifier
- 991019169547304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology