Kawazoe Y, Naka T, Fujimoto M, Kohzaki H, Morita Y, Narazaki M, Okumura K, Saitoh H, Nakagawa R, Uchiyama Y, Akira S, Kishimoto T
Department of Medicine III, Osaka University Medical School, Osaka, Japan.
J Exp Med. 2001 Jan 15;193(2):263-9. doi: 10.1084/jem.193.2.263.
Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1) is known to function as a negative feedback regulator of cytokine signaling, but it is unclear whether it is involved in other biological events. Here, we show that SSI-1 participates and plays an important role in the insulin signal transduction pathway. SSI-1-deficient mice showed a significantly low level of blood sugar. While the forced expression of SSI-1 reduced the phosphorylation level of insulin receptor substrate 1 (IRS-1), SSI-1 deficiency resulted in sustained phosphorylation of IRS-1 in response to insulin.Furthermore, SSI-1 achieves this inhibition both by binding directly to IRS-1 and by suppressing Janus kinases. These findings suggest that SSI-1 acts as a negative feedback factor also in the insulin signal transduction pathway through the suppression of IRS-1 phosphorylation.
信号转导与转录激活因子（STAT）诱导的STAT抑制因子1（SSI-1）作为细胞因子信号传导的负反馈调节因子已为人所知，但尚不清楚它是否参与其他生物学事件。在此，我们表明SSI-1参与胰岛素信号转导途径并发挥重要作用。SSI-1基因缺陷小鼠的血糖水平显著降低。虽然SSI-1的强制表达降低了胰岛素受体底物1（IRS-1）的磷酸化水平，但SSI-1缺陷导致IRS-1在胰岛素刺激下持续磷酸化。此外，SSI-1通过直接与IRS-1结合以及抑制Janus激酶来实现这种抑制作用。这些发现表明，SSI-1也通过抑制IRS-1磷酸化在胰岛素信号转导途径中作为负反馈因子发挥作用。
