Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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COS Cells
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DNA-Binding Proteins / analysis*
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Down-Regulation
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Intracellular Signaling Peptides and Proteins
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Mice
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Milk Proteins*
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatases / analysis*
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Protein Tyrosine Phosphatases / chemistry
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism
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SH2 Domain-Containing Protein Tyrosine Phosphatases
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STAT5 Transcription Factor
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Substrate Specificity
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Trans-Activators / analysis*
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism
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src Homology Domains
Substances
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DNA-Binding Proteins
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Intracellular Signaling Peptides and Proteins
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Milk Proteins
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STAT5 Transcription Factor
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Stat5a protein, mouse
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Trans-Activators
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatases
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Ptpn11 protein, mouse
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SH2 Domain-Containing Protein Tyrosine Phosphatases