Cutting edge: selective tyrosine dephosphorylation of interferon-activated nuclear STAT5 by the VHR phosphatase.
Cytokine-induced tyrosine phosphorylation of the transcription factor STAT5 is required for its transcriptional activity. In this article we show that the small dual-specificity phosphatase VHR selectively dephosphorylates IFN-alpha- and beta-activated, tyrosine-phosphorylated STAT5, leading to the subsequent inhibition of STAT5 function. Phosphorylation of VHR at Tyr(138) was required for its phosphatase activity toward STAT5. In addition, the Src homology 2 domain of STAT5 was required for the effective dephosphorylation of STAT5 by VHR. The tyrosine kinase Tyk2, which mediates the phosphorylation of STAT5, was also responsible for the phosphorylation of VHR at Tyr(138).
Hoyt
Richard
R
Division of Biological Sciences, University of California La Jolla, CA 92093, USA.
Zhu
Wei
W
Cerignoli
Fabio
F
Alonso
Andres
A
Mustelin
Tomas
T
David
Michael
M
D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D054640:Dual Specificity Phosphatase 3; D006367:HeLa Cells; D006801:Humans; D016898:Interferon-alpha / Q000502:physiology*; D016899:Interferon-beta / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism / Q000502:physiology*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*