دورية أكاديمية
IGF-1R modulation of acute GH-induced STAT5 signaling: role of protein tyrosine phosphatase activity
| العنوان: | IGF-1R modulation of acute GH-induced STAT5 signaling: role of protein tyrosine phosphatase activity |
|---|---|
| المؤلفون: | Gan, Yujun, Zhang, Yue, Buckels, Ashiya, Paterson, Andrew J., Jiang, Jing, Clemens, Thomas L., Zhang, Zhong-Yin, Du, Keyong, Chang, Yingzi, Frank, Stuart J. |
| المساهمون: | Biochemistry & Molecular Biology, School of Medicine |
| المصدر: | PMC |
| بيانات النشر: | Endocrine Society |
| سنة النشر: | 2013 |
| المجموعة: | Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| مصطلحات موضوعية: | Animals, Benzofurans -- pharmacology, Cells, Cultured, Growth Hormone -- physiology, Humans, Janus Kinase 2 -- metabolism, Mice, Transgenic, Nuclear Proteins -- genetics, Nuclear Proteins -- metabolism, Osteoblasts -- metabolism, Phosphorylation, Protein Processing, Post-Translational, Protein Tyrosine Phosphatase, Non-Receptor Type 1 -- antagonists & inhibitors, Non-Receptor Type 1 -- metabolism, Quinolines -- pharmacology, Receptor, IGF Type 1 -- metabolism, STAT5 Transcription Factor -- metabolism, Ubiquitin-Protein Ligases -- genetics, Ubiquitin-Protein Ligases -- metabolism |
| الوصف: | GH is a potent anabolic and metabolic factor that binds its cell surface receptor (GHR), activating the GHR-associated tyrosine kinase, Janus kinase 2, which phosphorylates and activates the latent transcription factor, signal transducer and activator of transcription 5 (STAT5). Some GH actions are mediated by the elaboration of IGF-1, which exerts effects by binding and activating the heterotetrameric tyrosine kinase growth factor receptor, IGF-1R. In addition to this GH-GHR-IGF-1-IGF-1R scheme, we have demonstrated in primary osteoblasts and in islet β-cells that then deletion or silencing of IGF-1R results in diminished GH-induced STAT5 phosphorylation, suggesting that the presence of IGF-1R may facilitate GH signaling. In this study, we explore potential roles for protein tyrosine phosphatase activity in modulating GH-induced signaling, comparing conditions in which IGF-1R is present or diminished. We confirm that in mouse primary osteoblasts harboring loxP sites flanking the IGF-1R gene, infection with an adenovirus that expresses the Cre recombinase results in IGF-1R deletion and diminished acute GH-induced STAT5 phosphorylation. Furthermore, we present a new model of IGF-1R silencing, in which expression of short hairpin RNA directed at IGF-1R greatly reduces IGF-1R abundance in LNCaP human prostate cancer cells. In both models, treatment with a chemical inhibitor of protein tyrosine phosphatase-1B (PTP-1B), but not one of src homology region 2 domain-containing phosphotase-1 (SHP-1) and SHP-2, reverses the loss of GH-induced STAT5 phosphorylation in cells lacking IGF-1R but has no effect in cells with intact IGF-1R. Furthermore, expression of either a dominant-negative PTP-1B or the PTP-1B-interacting inhibitory protein, constitutive photomorphogenesis 1, also rescues acute GH-induced STAT5 signaling in IGF-1R-deficient cells but has no effect in IGF-1R replete cells. By expressing a substrate-trapping mutant PTP-1B, we demonstrate that tyrosine phosphorylated Janus kinase-2 is a PTP-1B substrate only in ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Molecular Endocrinology; Gan, Y., Zhang, Y., Buckels, A., Paterson, A. J., Jiang, J., Clemens, T. L., … Frank, S. J. (2013). IGF-1R Modulation of Acute GH-Induced STAT5 Signaling: Role of Protein Tyrosine Phosphatase Activity. Molecular Endocrinology, 27(11), 1969–1979. http://doi.org/10.1210/me.2013-1178Test; https://hdl.handle.net/1805/6940Test |
| الإتاحة: | https://doi.org/10.1210/me.2013-1178Test https://hdl.handle.net/1805/6940Test |
| حقوق: | Publisher Policy |
| رقم الانضمام: | edsbas.5104FCCF |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |