Identification of Protein Tyrosine Phosphatases with Specificity for the Ligand-Activated Growth Hormone Receptor
| Autor: | Rob Hooft van Huijsduijnen, Fabrizio Arigoni, Ger J. Strous, Christian Pasquali, Xavier Espanel, Mireille Guerrier, Sébastien Wälchli, Marie Laure Curchod |
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| Rok vydání: | 2003 |
| Předmět: |
animal structures
Molecular Sequence Data CHO Cells Protein tyrosine phosphatase Growth hormone receptor Biology Ligands SH2 domain environment and public health Cell Line Substrate Specificity chemistry.chemical_compound Endocrinology Cricetinae Animals Humans Protein phosphorylation Amino Acid Sequence Phosphotyrosine Receptor Molecular Biology Tyrosine phosphorylation Receptors Somatotropin General Medicine enzymes and coenzymes (carbohydrates) Biochemistry chemistry Organ Specificity Growth Hormone Tyrosine Phosphorylation Protein Tyrosine Phosphatases Signal transduction hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Molecular Endocrinology. 17:2228-2239 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | Protein tyrosine phosphatases (PTPs) play key roles in switching off tyrosine phosphorylation cascades, such as initiated by cytokine receptors. We have used substrate-trapping mutants of a large set of PTPs to identify members of the PTP family that have substrate specificity for the phosphorylated human GH receptor (GHR) intracellular domain. Among 31 PTPs tested, T cell (TC)-PTP, PTP-beta, PTP1B, stomach cancer-associated PTP 1 (SAP-1), Pyst-2, Meg-2, and PTP-H1 showed specificity for phosphorylated GHR that had been produced by coexpression with a kinase in bacteria. We then used GH-induced, phosphorylated GH receptor, purified from overexpressing mammalian cells, in a Far Western-based approach to test whether these seven PTPs were also capable of recognizing ligand-induced, physiologically phosphorylated GHR. In this assay, only TC-PTP, PTP1B, PTP-H1, and SAP-1 interacted with the mature form of the phosphorylated GHR. In parallel, we show that these PTPs recognize very different subsets of the seven GHR tyrosines that are potentially phosphorylated. Finally, mRNA tissue distribution of these PTPs by RT-PCR analysis and coexpression of the wild-type PTPs to test their ability to dephosphorylate ligand-activated GHR suggest PTP-H1 and PTP1B as potential candidates involved in GHR signaling. |
| Databáze: | OpenAIRE |
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