Nakahira Masakiyo, Tanaka Takashi, Robson Bryanne E, Mizgerd Joseph P, Grusby Michael J
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Immunity. 2007 Feb;26(2):163-76. doi: 10.1016/j.immuni.2007.01.010.
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.
信号转导与转录激活因子（STAT）蛋白是一类潜在的细胞质转录因子家族，在细胞因子刺激后通过酪氨酸磷酸化被激活。STAT信号传导的一种调节机制是通过蛋白酪氨酸磷酸酶（PTP）的作用进行去磷酸化。我们已鉴定出嗜碱性粒细胞样蛋白酪氨酸磷酸酶（PTP-BL）为一种STAT磷酸酶。PTP-BL在体外和体内使STAT蛋白去磷酸化，导致STAT介导的基因激活减弱。在CD4(+) T细胞中，PTP-BL缺陷导致STAT4和STAT6的激活增加且持续时间延长，从而增强辅助性T细胞1（Th1）和辅助性T细胞2（Th2）的分化。综上所述，我们的研究结果表明PTP-BL是STAT信号通路在生理上重要的负调节因子。
