重复IGFBP-2基因的硬骨鱼鱼:蛋白质结构和功能保护和基因表达差异。
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段周J,李W,龟井静香H, C
重复IGFBP-2基因的硬骨鱼鱼:蛋白质结构和功能保护和基因表达差异。
《公共科学图书馆•综合》。2008;3 (12):e3926。doi: 10.1371 / journal.pone.0003926。Epub 2008年12月12日。
- PubMed ID
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19081843 (在PubMed]
- 文摘
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背景:胰岛素样生长因子结合protein-2 (IGFBP-2)是一种分泌蛋白结合并调节IGF行动在控制增长,开发、复制、和老化。表达升高IGFBP-2通常与发展有关的许多类型的癌症。方法/主要结果:我们报告两个IGFBP-2的识别和表征基因在斑马鱼和其他四个硬骨鱼类的鱼。比较基因组学和结构分析表明,它们是人类IGFBP-2 co-orthologs基因。生化分析表明斑马鱼igfbp-2a和2 b编码分泌igf结合的蛋白质。这两个基因表现出明显的时空表达模式。在胚胎发生,IGFBP-2a mRNA最初发现的镜头,然后在大脑中边界脉管系统,随后变成了肝脏中高度表达。在成年阶段,肝脏IGFBP-2a mRNA水平最高,其次是大脑。低水平的IGFBP-2a信使rna被发现在肌肉和只在男性性腺的成年人。IGFBP-2b信使rna检测最初在所有组织在低水平,但后来变得丰富的肝脏中。 In adult males, IGFBP-2b mRNA is only detected in the liver. In adult females, it is also found in the gut, kidney, ovary, and muscle. To gain insights into how the IGFBP-2 genes may have evolved through partitioning of ancestral functions, functional and mechanistic studies were carried out. Expression of zebrafish IGFBP-2a and -2b caused significant decreases in the growth and developmental rates and their effects are comparable to that of human IGFBP-2. IGFBP-2 mutants with altered IGF binding-, RGD-, and heparin-binding sites were generated and their actions examined. While mutating the RGD and heparin binding sites had little effect, altering the IGF binding site abolished its biological activity. CONCLUSIONS/SIGNIFICANCE: These results suggest that IGFBP-2 is a conserved regulatory protein and it inhibits growth and development primarily by binding to and inhibiting IGF actions in vivo. The duplicated IGFBP-2 genes may provide additional flexibility in the regulation of IGF activities.