Cytosolic tyrosine dephosphorylation of STAT5. Potential role of SHP-2 in STAT5 regulation
| Autor: | C L, Yu, Y J, Jin, S J, Burakoff |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cell Nucleus
Protein Tyrosine Phosphatase Non-Receptor Type 6 Intracellular Signaling Peptides and Proteins Down-Regulation Biological Transport Protein Tyrosine Phosphatase Non-Receptor Type 11 Protein-Tyrosine Kinases Lymphoma T-Cell Milk Proteins Cell Line DNA-Binding Proteins Cytosol Protein Biosynthesis Mutation STAT5 Transcription Factor Trans-Activators Tumor Cells Cultured Interleukin-2 Phosphorylation Protein Tyrosine Phosphatases Phosphotyrosine Protein Binding |
| Zdroj: | The Journal of biological chemistry. 275(1) |
| ISSN: | 0021-9258 |
| Popis: | STAT5, a member of the signal transducers and activators of transcription (STATs), is important in modulating T cell functions through interleukin-2 (IL-2) receptors. Like other STAT proteins, STAT5 undergoes a rapid activation and inactivation cycle upon cytokine stimulation. Tyrosine phosphorylation and dephosphorylation are critical in regulating STAT5 activity. A number of protein tyrosine kinases have been shown to phosphorylate STAT5; however, the phosphatases responsible for STAT5 dephosphorylation remain unidentified. Using CTLL-20 as a model system, we provide evidence that tyrosine dephosphorylation of STAT5 subsequent to IL-2-induced phosphorylation occurs in the absence of STAT5 nuclear translocation and new protein synthesis. Nevertheless, down-regulation of the upstream Janus kinase activity during the deactivation cycle of IL-2-induced signaling does involve new protein synthesis. These findings point to the constitutive presence of STAT5 tyrosine phosphatase activity in the cytosolic compartment. We further demonstrate that SHP-2, but not SHP-1, directly dephosphorylates STAT5 in an in vitro tyrosine phosphatase assay with purified proteins. Furthermore, tyrosine-phosphorylated STAT5 associates with the substrate-trapping mutant (Cys --Ser) of SHP-2 but not SHP-1. These results suggest a potential role for cytoplasmic protein-tyrosine phosphatases in directly dephosphorylating STAT proteins and in maintaining a basal steady state level of STAT activity. |
| Databáze: | OpenAIRE |
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