Identification of Shp-2 as a Stat5A phosphatase.
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.
Chen
Yuhong
Y
Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, Wisconsin 53226, USA.
Wen
Renren
R
Yang
Shoua
S
Schuman
James
J
Zhang
Eric E
EE
Yi
Taolin
T
Feng
Gen-Sheng
GS
Wang
Demin
D
D000818:Animals; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008894:Milk Proteins; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000032:analysis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D050799:STAT5 Transcription Factor; D013379:Substrate Specificity; D015534:Trans-Activators / Q000032:analysis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018909:src Homology Domains
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; D015534:Trans-Activators; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases