Regulation of signal transducer and activator of transcription signaling by the tyrosine phosphatase PTP-BL
Regulation of signal transducer and activator of transcription signaling by the tyrosine phosphatase PTP-BL
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DOI：
10.1016/j.immuni.2007.01.010
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发表时间：
2007-02-01
期刊：
影响因子：
32.4
通讯作者：
Grusby, Michael J.
中科院分区：
文献类型：
--
作者：
Nakahira, Masakiyo;Tanaka, Takashi;Grusby, Michael J.
信号转导和转录激活因子（STAT）蛋白是一类潜在的细胞质转录因子，在细胞因子刺激后被酪氨酸磷酸化激活。STAT信号被调节的一种机制是通过蛋白酪氨酸磷酸酶（PTP）的作用进行去磷酸化。我们已经确定PTP-嗜碱性粒细胞样（PTP- bl）为STAT PTP。PTP-BL在体内和体外都能使STAT蛋白去磷酸化，从而减弱STAT介导的基因激活。在CD4(+) T细胞中，PTP-BL缺乏导致STAT4和STAT6的激活增加和延长，从而增强T辅助1 （Th1）和Th2细胞分化。综上所述，我们的研究结果表明PTP-BL是STAT信号通路的生理上重要的负调节因子。
Signal Transducer and Activator of Transcription (STAT) proteins are a family of latent cytoplasmic transcription factors that are activated by tyrosine phosphorylation after cytokine stimulation. One mechanism by which STAT signaling is regulated is by dephosphorylation through the action of protein tyrosine phosphatases (PTP). We have identified PTP-Basophil like (PTP-BL) as a STAT PTP. PTP-BL dephosphorylates STAT proteins in vitro and in vivo, resulting in attenuation of STAT-mediated gene activation. In CD4(+) T cells, PTP-BL deficiency leads to increased and prolonged activation of STAT4 and STAT6, and consequently enhanced T helper 1 (Th1) and Th2 cell differentiation. Taken together, our findings demonstrate that PTP-BL is a physiologically important negative regulator of the STAT signaling pathway.