Jin Hong-Jian, Shao Jian-Zhong, Xiang Li-Xin
College of Life Sciences, Zhejiang University, Hangzhou 310012, People's Republic of China.
Mol Immunol. 2007 Feb;44(5):1042-51. doi: 10.1016/j.molimm.2006.03.003. Epub 2006 Apr 18.
The suppressor of cytokine signaling 3 (SOCS-3) is a member of a newly discovered protein family, which have been shown to regulate the responses of many immune cytokines, such as interferon (IFN), interleukin-2 (IL-2) and IL-6, etc., by inhibiting Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling in a negative auto-regulatory manner. Although SOCS-3 was well characterized in several mammal species, there was still no report in fish. In present study, we initially identified and characterized the SOCS-3 genes from three fishes, the Tetraodon nigroviridis, the Danio rerio and the Fugu rubripes. The results showed that Tetraodon SOCS-3 gene located within a 2666 bp genomic fragment of chromosome 3, transcribed into a 1445 bp mRNA including 273 bp 5' UTR (untranslated region), 606 bp ORF (open reading frame) and 566 bp 3' UTR. Tetraodon SOCS-3 with 201aa (amino acid) has a calculated molecular mass of 22.76 kDa and a theoretical pI of 8.99. Danio SOCS-3 gene located within a 3617 bp genomic fragment of chromosome 3, transcribed into a 1927 bp mRNA including 178 bp 5' UTR, 624 bp ORF and 1125 bp 3' UTR. Danio SOCS-3 with 207aa has a calculated molecular mass of 23.68 kDa and a theoretical pI of 9.19. Fugu SOCS-3 gene located within a 2842 bp genomic fragment of Scaffold_1118, transcribed into a 1528 bp mRNA including 209 bp 5' UTR, 606 bp ORF and 713 bp 3' UTR. Fugu SOCS-3 with 201aa has a calculated molecular mass of 22.76 kDa and a theoretical pI of 8.18. The fish SOCS-3-encoding genes with the same organization as the mammalians consist of two exons and a single intron that lies in the 5' UTR of the transcript. The deduced amino acid sequences of the fish SOCS-3s showed: 60.7-61.7% sequence identity to mammalian SOCS-3s; 62.3-63.2% sequence identity to bird SOCS-3s; and 55.3-57.8% sequence identity to amphibian SOCS-3s. Phylogenetic analysis separates the fish SOCS-3s into an exclusive group. Expression study of Tetraodon SOCS-3 mRNA in ten selected tissues showed that it was constitutively expressed and induced by lipopolysaccharide (LPS) strikingly. These results indicated that SOCS-3s in fish may be involved in inflammatory responses. This is the first report of cloning and characterization of SOCS-3 cDNAs and genes in fish.
细胞因子信号转导抑制因子3（SOCS-3）是新发现的蛋白质家族成员，已证明其可通过以负性自调节方式抑制Janus激酶（JAK）-信号转导子和转录激活子（STAT）信号传导，来调控多种免疫细胞因子的反应，如干扰素（IFN）、白细胞介素-2（IL-2）和IL-6等。尽管SOCS-3在几种哺乳动物中已得到充分研究，但在鱼类中尚无相关报道。在本研究中，我们首次从三种鱼类——暗绿鲀、斑马鱼和红鳍东方鲀中鉴定并表征了SOCS-3基因。结果表明，暗绿鲀SOCS-3基因位于3号染色体上一个2666 bp的基因组片段内，转录成一个1445 bp的mRNA，包括273 bp的5'非翻译区（UTR）、606 bp的开放阅读框（ORF）和566 bp的3'UTR。暗绿鲀SOCS-3含201个氨基酸（aa），计算分子量为22.76 kDa，理论等电点为8.99。斑马鱼SOCS-3基因位于3号染色体上一个3617 bp的基因组片段内，转录成一个1927 bp的mRNA，包括178 bp的5'UTR、624 bp的ORF和1125 bp的3'UTR。斑马鱼SOCS-3含207个aa，计算分子量为23.68 kDa，理论等电点为9.19。红鳍东方鲀SOCS-3基因位于Scaffold_1118的一个2842 bp基因组片段内，转录成一个1528 bp的mRNA，包括209 bp的5'UTR、606 bp的ORF和713 bp的3'UTR。红鳍东方鲀SOCS-3含201个aa，计算分子量为22.76 kDa，理论等电点为8.18。鱼类中编码SOCS-3的基因与哺乳动物的结构相同，由两个外显子和一个位于转录本5'UTR的单一内含子组成。推导的鱼类SOCS-3氨基酸序列显示：与哺乳动物SOCS-3的序列同一性为60.7%-61.7%；与鸟类SOCS-3的序列同一性为62.3%-63.2%；与两栖动物SOCS-3的序列同一性为55.3%-57.8%。系统发育分析将鱼类SOCS-3分为一个独立的类群。对暗绿鲀SOCS-3 mRNA在十个选定组织中的表达研究表明，它组成性表达且受到脂多糖（LPS）的显著诱导。这些结果表明鱼类中的SOCS-3可能参与炎症反应。这是鱼类中SOCS-3 cDNA和基因克隆与表征的首次报道。
