Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
Fish Shellfish Immunol. 2010 Feb;28(2):362-71. doi: 10.1016/j.fsi.2009.11.012. Epub 2009 Dec 16.
As a member of a newly discovered protein family, the suppressor of cytokine signalling 3 (SOCS-3) has been shown to regulate the responses of many immune cytokines in a negative auto-regulatory manner. The full-length cDNA of common carp SOCS-3 was 1603 bp and contained a 630 bp open reading frame (ORF) coding for a protein of 209 amino acids. Carp SOCS-3 molecule was well conserved especially in the SRC homology 2 (SH2) and the SOCS box. The kinase inhibitory region (KIR) and ESS domains, upstream of the SH2 domain, were conserved in carp SOCS-3, except for a specific insertion (PHRYK) in the KIR domain at the N-terminal region. Three conserved cysteine (Cys-102, 124 and 193) residues, and one additional cysteine (Cys-168) residue, were also found in carp SOCS-3. The 2015 bp genomic DNA of carp SOCS-3 contained two exons and one intron. Phylogenetic analysis showed that carp SOCS-3 sequence grouped with other known fish SOCS-3 sequences with zebrafish SOCS-3 as the closest neighbour. RT-PCR analysis showed that carp SOCS-3 was initially expressed at 4 h pf (post-fertilization) and gradually increased up to 4 w pf during embryogenesis. By RT-qPCR analysis, carp SOCS-3 gene was predominantly detected in gill, head kidney, thymus and skin, followed by spleen and peripheral blood, lower expression level was detected in kidney, intestine, liver and muscle; the SOCS-3 transcript was significantly increased in thymus, head kidney, spleen and intestine of GH (growth hormone)-transgenic carp; after SVCV (spring viraemia of carp virus) infection, the carp SOCS-3 transcript was significantly up-regulated in gill, intestine, thymus, spleen, head kidney and kidney tissues in a time-dependent manner. These results suggest that teleost SOCS-3 may play an active role in the modulation of viral-induced innate immune response and in preventing the overaction of some cytokines with viral stimulation.
作为新发现的蛋白质家族的一员，细胞因子信号转导抑制因子 3（SOCS-3）已被证明以负反馈的方式调节许多免疫细胞因子的反应。鲤鱼 SOCS-3 的全长 cDNA 为 1603bp，包含一个 630bp 的开放阅读框（ORF），编码 209 个氨基酸的蛋白质。鲤鱼 SOCS-3 分子在结构上高度保守，尤其是在 SH2 结构域和 SOCS 盒。SH2 结构域上游的激酶抑制区（KIR）和 ESS 结构域在鲤鱼 SOCS-3 中保守，除了在 N 端区域的 KIR 结构域中有一个特定的插入（PHRYK）。鲤鱼 SOCS-3 中还发现了三个保守的半胱氨酸（Cys-102、124 和 193）残基和一个额外的半胱氨酸（Cys-168）残基。鲤鱼 SOCS-3 的 2015bp 基因组 DNA 包含两个外显子和一个内含子。系统进化分析表明，鲤鱼 SOCS-3 序列与其他已知鱼类 SOCS-3 序列聚类，与斑马鱼 SOCS-3 关系最密切。RT-PCR 分析表明，鲤鱼 SOCS-3 在受精后 4 小时（pf）开始表达，并在胚胎发生期间逐渐增加到 4 周 pf。通过 RT-qPCR 分析，鲤鱼 SOCS-3 基因主要在鳃、头肾、胸腺和皮肤中检测到，其次是脾脏和外周血，在肾脏、肠道、肝脏和肌肉中检测到较低的表达水平；在 GH（生长激素）转基因鲤鱼的胸腺、头肾、脾脏和肠道中，SOCS-3 转录物显著增加；在 SVCV（鲤鱼病毒性出血病病毒）感染后，鲤鱼 SOCS-3 转录物在鳃、肠、胸腺、脾脏、头肾和肾脏组织中随时间呈显著上调。这些结果表明，硬骨鱼类 SOCS-3 可能在调节病毒诱导的先天免疫反应和防止某些细胞因子在病毒刺激下过度作用方面发挥积极作用。
