Sato Noriko, Kawai Taro, Sugiyama Kenji, Muromoto Ryuta, Imoto Seiyu, Sekine Yuichi, Ishida Masato, Akira Shizuo, Matsuda Tadashi
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan.
Int Immunol. 2005 Dec;17(12):1543-52. doi: 10.1093/intimm/dxh331. Epub 2005 Oct 11.
Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor that can be activated by cytokines and growth factors. It plays important roles in cell growth, apoptosis and cell transformation, and is constitutively active in a variety of tumor cells. In this study, we provide evidence that zipper-interacting protein kinase (ZIPK) interacts physically with STAT3. ZIPK specifically interacted with STAT3, and did not bind to STAT1, STAT4, STAT5a, STAT5b or STAT6. ZIPK phosphorylated STAT3 on serine 727 (Ser727) and enhanced STAT3 transcriptional activity. Small interfering RNA-mediated reduction of ZIPK expression decreased leukemia inhibitory factor (LIF)- and IL-6-induced STAT3-dependent transcription. Furthermore, LIF- and IL-6-mediated STAT3 activation stimulated ZIPK activity. Taken together, our data suggest that ZIPK interacts with STAT3 within the nucleus to regulate the transcriptional activity of STAT3 via phosphorylation of Ser727.
信号转导与转录激活因子3（STAT3）是一种潜在的细胞质转录因子，可被细胞因子和生长因子激活。它在细胞生长、凋亡和细胞转化中发挥重要作用，并且在多种肿瘤细胞中持续激活。在本研究中，我们提供证据表明拉链相互作用蛋白激酶（ZIPK）与STAT3发生物理相互作用。ZIPK特异性地与STAT3相互作用，而不与STAT1、STAT4、STAT5a、STAT5b或STAT6结合。ZIPK使STAT3的丝氨酸727（Ser727）磷酸化并增强STAT3转录活性。小干扰RNA介导的ZIPK表达降低减少了白血病抑制因子（LIF）和IL-6诱导的STAT3依赖性转录。此外，LIF和IL-6介导的STAT3激活刺激了ZIPK活性。综上所述，我们的数据表明ZIPK在细胞核内与STAT3相互作用，通过Ser727磷酸化调节STAT3的转录活性。
