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) 101 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 DAuthors
Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinRenren Wen PhD Adjunct Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin
MESH 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
