Jak2 is essential for signaling through a variety of cytokine receptors
Jak2 is essential for signaling through a variety of cytokine receptors
复制标题
DOI：
10.1016/s0092-8674(00)81167-8
复制
发表时间：
1998-05-01
期刊：
影响因子：
64.5
通讯作者：
Ihle, JN
中科院分区：
文献类型：
--
作者：
Parganas, E;Wang, D;Ihle, JN
多种细胞因子激活Janus蛋白酪氨酸激酶家族（Jaks）的受体相关成员。为了评估Jak 2的作用，我们衍生了Jak 2缺陷小鼠。该突变由于缺乏确定性红细胞生成而导致胚胎死亡。胎儿肝髓样祖细胞，虽然存在基于谱系特异性标志物的表达，但不能对促红细胞生成素、促血小板生成素、白细胞介素-3（IL-3）或粒细胞/巨噬细胞集落刺激因子作出反应。相反，对粒细胞特异性集落刺激因子的反应不受影响。Jak 2缺陷型成纤维细胞对干扰素γ（IFN γ）无反应，但对IFN α/β和IL-6的反应不受影响。最后，重建实验表明，Jak 2是不需要的淋巴祖细胞的产生，其扩增，或功能分化。因此，Jak 2在一组特定的细胞因子受体的功能中起着关键的、非冗余的作用。
A variety of cytokines activate receptor-associated members of the Janus family of protein tyrosine kinases (Jaks). To assess the role of Jak2, we have derived Jak2-deficient mice. The mutation causes an embryonic lethality due to the absence of definitive erythropoiesis. Fetal liver myeloid progenitors, although present based on the expression of lineage specific markers, fail to respond to erythropoietin, thrombopoietin, interleukin-3 (IL-3), or granulocyte/macrophage colony-stimulating factor. In contrast, the response to granulocyte specific colony-stimulating factor is unaffected. Jak2-deficient fibroblasts failed to respond to interferon gamma (IFN gamma), although the responses to IFN alpha/beta and IL-6 were unaffected. Lastly, reconstitution experiments demonstrate that Jak2 is not required for the generation of lymphoid progenitors, their amplification, or functional differentiation. Therefore, Jak2 plays a critical, nonredundant role in the function of a specific group of cytokines receptors.