SOCS1的交叉调节GM-CSF信号的能力是剂量依赖的
Grace M Bidgood1,2, Narelle Keating1,2, Lizeth Meza Guzman1,2
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
概括
细胞因子信号传递抑制剂1 (SOCS1) 调节免疫反应. 这项研究表明,SOCS1需要一个关键的表达水平来抑制干扰素-马信号传递,具有选择性途径调节.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 细胞因子信号传递抑制剂1 (SOCS1) 是细胞因子信号传递途径的关键负调节器,包括Janus酶信号转换器和转录激活器 (JAK-STAT) 途径.
- 了解SOCS1的时间动力学和选择性调节对于理解由干扰素 (IFN) 和白细胞间蛋白 (IL) 等细胞因子介导的免疫反应至关重要.
研究的目的:
- 为了研究SOCS1在活细胞中对细胞因子的实时诱导.
- 通过SOCS1.1,确定不同信号通路的选择性调节.
- 建立一个小鼠模型来研究内源控制下的SOCS1动态.
主要方法:
- 在内源性Socs1促进体下生成表达Halo-tag-SOCS1融合蛋白的小鼠模型.
- 在IFNγ和IL-4刺激后,分析来自Halo-Socs1小鼠的巨细胞中SOCS1表达的分析.
- 评估SOCS1对IFNγ和粒细胞巨细胞殖民地刺激因子 (GM-CSF) 的反应中的JAK-STAT信号抑制.
主要成果:
- 同卵性Halo-SOCS1小鼠在轻微的T细胞异常下是可行的,这可能是由于提摩细胞的增强表达.
- IFNγ和IL-4成功诱导了巨细胞中的Halo-SOCS1表达.
- 为了抑制IFNγ和GM-CSF驱动的JAK-STAT信号,需要SOCS1表达的临界值.
- IFNγ初始化并没有对IL-4信号进行交叉调节,这表明有选择性的通路控制.
结论:
- SOCS1需要表达超过关键值,以有效抑制IFNγ信号传递.
- SOCS1表现出细胞因子信号通路的选择性调节,尽管确切的机制尚未完全阐明.
- 开发的Halo-SOCS1小鼠模型为研究SOCS1活体动态和功能提供了有价值的工具.
更多相关视频
07:45A Cell Free Assay System Estimating the Neutralizing Capacity of GM-CSF Antibody using Recombinant Soluble GM-CSF Receptor
Published on: June 27, 2011
12.7K
10:27In Vitro Differentiation of Mouse Granulocyte-macrophage-colony-stimulating Factor GM-CSF-producing T Helper THGM Cells
Published on: September 10, 2018
7.2K
相关概念视频
Regulation of Hematopoietic Stem Cells
3.1K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.1K
TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
Assembly of Signaling Complexes
5.7K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.7K
Pleiotropy
39.7K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
39.7K
Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K
The JAK-STAT Signaling Pathway
8.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.7K
