Protein-tyrosine Phosphatase H1 Controls Growth Hormone Receptor Signaling and Systemic Growth
| Autor: | Marie-Laure Curchod, Paola Zaratin, David M. Valenzuela, Yingzi Xue, Ann M. Clark, Dominique Perrin, Claudia Patrignani, Maria Chiara Magnone, Rob Hooft van Huijsduijnen, R Pescini, Iwona Pilecka, Jason Yasenchak, Christian Rommel |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Phosphatase Growth hormone receptor Biology Models Biological Biochemistry Mice Growth factor receptor In vivo Catalytic Domain Internal medicine medicine Animals Humans Growth factor receptor inhibitor RNA Messenger Insulin-Like Growth Factor I Phosphorylation Molecular Biology Cell Proliferation Insulin-like growth factor 1 receptor Mice Knockout Growth factor Protein Tyrosine Phosphatase Non-Receptor Type 3 Wild type Receptors Somatotropin Cell Biology Endocrinology Liver Mutation Female Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 282:35405-35415 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m705814200 |
| Popis: | Several protein-tyrosine phosphatases (PTPs) have been implicated in the control of growth hormone receptor (GHR) signaling, but none have been shown to affect growth in vivo. We have applied a battery of molecular and cellular approaches to test a family-wide panel of PTPs for interference with GHR signaling. Among the subset of PTPs that showed activity in multiple readouts, we selected PTP-H1/PTPN3 for further in vivo studies and found that mice lacking the PTP-H1 catalytic domain show significantly enhanced growth over their wild type littermates. In addition, PTP-H1 mutant animals had enhanced plasma and liver mRNA expression of insulin-like growth factor 1, as well as increased bone density and mineral content. These observations point to a controlling role for PTP-H1 in modulating GHR signaling and systemic growth through insulin-like growth factor 1 secretion. |
| Databáze: | OpenAIRE |
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