Cutting edge: Selective tyrosine dephosphorylation of interferon-activated nuclear STAT5 by the VHR phosphatase
Cutting edge: Selective tyrosine dephosphorylation of interferon-activated nuclear STAT5 by the VHR phosphatase
复制标题
DOI：
10.4049/jimmunol.179.6.3402
复制
发表时间：
2007-09-15
影响因子：
4.4
通讯作者：
David, Michael
中科院分区：
文献类型：
--
作者：
Hoyt, Richard;Zhu, Wei;David, Michael
转录因子STAT 5的转录活性需要细胞因子诱导的酪氨酸磷酸化。在这篇文章中，我们表明，小的双特异性磷酸酶VHR选择性地去磷酸化IFN-α和β-激活，酪氨酸磷酸化的STAT 5，导致随后的抑制STAT 5的功能。VHR在Tyr（138）处的磷酸化是其对STAT 5的磷酸酶活性所必需的。此外，STAT 5的Src同源2结构域是VHR对STAT 5的有效去磷酸化所必需的。介导STAT 5磷酸化的酪氨酸激酶Tyk 2也负责VHR在Tyr处的磷酸化（138）。
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).