Identification of Shp-2 as a Stat5A phosphatase. J Biol Chem 2003 May 09;278(19):16520-7
Date
03/05/2003Pubmed ID
12615921DOI
10.1074/jbc.M210572200Scopus ID
2-s2.0-0037593839 (requires institutional sign-in at Scopus site) 102 CitationsAbstract
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.
Author List
Chen Y, Wen R, Yang S, Schuman J, Zhang EE, Yi T, Feng GS, Wang DMESH terms used to index this publication - Major topics in bold
AnimalsCOS Cells
DNA-Binding Proteins
Down-Regulation
Intracellular Signaling Peptides and Proteins
Mice
Milk Proteins
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatases
SH2 Domain-Containing Protein Tyrosine Phosphatases
STAT5 Transcription Factor
Substrate Specificity
Trans-Activators
src Homology Domains
