Shimoda K, Kato K, Aoki K, Matsuda T, Miyamoto A, Shibamori M, Yamashita M, Numata A, Takase K, Kobayashi S, Shibata S, Asano Y, Gondo H, Sekiguchi K, Nakayama K, Nakayama T, Okamura T, Okamura S, Niho Y, Nakayama K
Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Immunity. 2000 Oct;13(4):561-71. doi: 10.1016/s1074-7613(00)00055-8.
Janus kinases (Jaks) play an important role in signal transduction via cytokine receptors. Tyk2 is a Janus kinase, and we developed tyk2-deficient mice to study the requirement for tyk2 in vivo. Tyk2-deficient mice show no overt developmental abnormalities; however, they display a lack of responsiveness to a small amount of IFNalpha, although a high concentration of IFNalpha can fully transduce its signal even in the absence of tyk2. Furthermore, IL-12-induced T cell function is defective in these mice. In contrast, these mice respond normally to IL-6 and IL-10, both of which activate tyk2 in vitro. These observations demonstrate that tyk2 plays only a restricted role in mediating IFNalpha-dependent signaling while being required in mediating IL-12-dependent biological responses.
Janus激酶（Jaks）在通过细胞因子受体进行的信号转导中发挥重要作用。酪氨酸激酶2（Tyk2）是一种Janus激酶，我们培育了Tyk2基因缺陷型小鼠，以研究体内对Tyk2的需求。Tyk2基因缺陷型小鼠未表现出明显的发育异常；然而，它们对少量的干扰素α（IFNα）缺乏反应，尽管高浓度的IFNα即使在没有Tyk2的情况下也能完全传导其信号。此外，在这些小鼠中，白细胞介素12（IL-12）诱导的T细胞功能存在缺陷。相比之下，这些小鼠对IL-6和IL-10反应正常，这两种细胞因子在体外均可激活Tyk2。这些观察结果表明，Tyk2在介导IFNα依赖性信号传导中仅起有限作用，而在介导IL-12依赖性生物学反应中是必需的。
