Cytosolic tyrosine dephosphorylation of STAT5. Potential role of SHP-2 in STAT5 regulation.
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.
Mesh Terms:
Biological Transport, Cell Line, Cell Nucleus, Cytosol, DNA-Binding Proteins, Down-Regulation, Interleukin-2, Intracellular Signaling Peptides and Proteins, Lymphoma, T-Cell, Milk Proteins, Mutation, Phosphorylation, Phosphotyrosine, Protein Binding, Protein Biosynthesis, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Protein-Tyrosine Kinases, STAT5 Transcription Factor, Trans-Activators, Tumor Cells, Cultured
Biological Transport, Cell Line, Cell Nucleus, Cytosol, DNA-Binding Proteins, Down-Regulation, Interleukin-2, Intracellular Signaling Peptides and Proteins, Lymphoma, T-Cell, Milk Proteins, Mutation, Phosphorylation, Phosphotyrosine, Protein Binding, Protein Biosynthesis, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Protein-Tyrosine Kinases, STAT5 Transcription Factor, Trans-Activators, Tumor Cells, Cultured
J. Biol. Chem.
Date: Jan. 07, 2000
PubMed ID: 10617656
View in: Pubmed Google Scholar
Download Curated Data For This Publication
4989
Switch View:
- Interactions 5