干扰素-γ 是细胞因子诱导分化的主检查点调节剂。
Interferon-γ is a master checkpoint regulator of cytokine-induced differentiation.
机构信息
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.
Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037.
出版信息
Proc Natl Acad Sci U S A. 2017 Aug 15;114(33):E6867-E6874. doi: 10.1073/pnas.1706915114. Epub 2017 Jul 31.
Abstract
Cytokines are protein mediators that are known to be involved in many biological processes, including cell growth, survival, inflammation, and development. To study their regulation, we generated a library of 209 different cytokines. This was used in a combinatorial format to study the effects of cytokines on each other, with particular reference to the control of differentiation. This study showed that IFN-γ is a master checkpoint regulator for many cytokines. It operates via an autocrine mechanism to elevate STAT1 and induce internalization of gp130, a common component of many heterodimeric cytokine receptors. This targeting of a receptor subunit that is common to all members of an otherwise diverse family solves the problem of how a master regulator can control so many diverse receptors. When one adds an autocrine mechanism, fine control at the level of individual cells is achieved.
摘要
细胞因子是已知参与许多生物过程的蛋白质介质，包括细胞生长、存活、炎症和发育。为了研究它们的调节作用，我们生成了一个包含 209 种不同细胞因子的文库。这些细胞因子以组合的形式被用于研究它们之间的相互作用，特别关注分化的控制。这项研究表明，IFN-γ 是许多细胞因子的主检查点调节剂。它通过自分泌机制作用，提升 STAT1 并诱导 gp130 的内化，gp130 是许多异二聚体细胞因子受体的共同组成部分。这种针对受体亚基的靶向作用，该亚基是一个多样化家族中所有成员的共同组成部分，解决了主调节剂如何控制如此多的不同受体的问题。当添加自分泌机制时，就可以在单个细胞的水平上实现精细控制。
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