Identification of Shp-2 as a Stat5A Phosphatase
| Autor: | James Schuman, Renren Wen, Yuhong Chen, Shoua Yang, Taolin Yi, Eric E. Zhang, Demin Wang, Gen-Sheng Feng |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
SH2 Domain-Containing Protein Tyrosine Phosphatases
animal structures Phosphatase Down-Regulation Protein Tyrosine Phosphatase Non-Receptor Type 11 chemical and pharmacologic phenomena Protein tyrosine phosphatase Biology Biochemistry Substrate Specificity src Homology Domains Dephosphorylation Mice chemistry.chemical_compound In vivo Transcription (biology) STAT5 Transcription Factor Animals Tyrosine Molecular Biology COS cells Intracellular Signaling Peptides and Proteins food and beverages hemic and immune systems Tyrosine phosphorylation Cell Biology Milk Proteins DNA-Binding Proteins chemistry COS Cells embryonic structures Trans-Activators Protein Tyrosine Phosphatases |
| Zdroj: | Journal of Biological Chemistry. 278:16520-16527 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m210572200 |
| Popis: | Stat5A, a member of the signal transducers and activators of transcription (Stat) family, is activated upon a single tyrosine phosphorylation. Although much is known about the activation process, the mechanism by which the tyrosine-phosphorylated Stat5A proteins are inactivated is largely unknown. In this report, we demonstrate that down-regulation of the tyrosine-phosphorylated Stat5A was via dephosphorylation. Using tyrosine-phosphorylated peptides derived from Stat5A, we were able to purify protein-tyrosine phosphatase Shp-2 from cell lysates. Shp-2, but not Shp-1, specifically interacted with Stat5A in vivo, and the interaction was tyrosine phosphorylation-dependent. Moreover, Shp-2 was able to accelerate Stat5A dephosphorylation, and dephosphorylation of Stat5A was dramatically delayed in Shp-2-deficient cells. Therefore, we conclude that Shp-2 is a Stat5A phosphatase, which down-regulates the active Stat5A in vivo. |
| Databáze: | OpenAIRE |
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