EVOLUTION OF THE INSULIN SUPERFAMILY - CLONING OF A HYBRID INSULIN INSULIN-LIKE GROWTH-FACTOR CDNA FROM AMPHIOXUS

EVOLUTION OF THE INSULIN SUPERFAMILY - CLONING OF A HYBRID INSULIN INSULIN-LIKE GROWTH-FACTOR CDNA FROM AMPHIOXUS
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DOI:
10.1073/pnas.87.23.9319
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发表时间:
1990-12-01
影响因子:
11.1
通讯作者:
STEINER, DF
STEINER, DF
中科院分区:
综合性期刊1区
文献类型:
--
作者:
CHAN, SJ;CAO, QP;STEINER, DF

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尽管胰岛素和胰岛素样生长因子(IGF)在氨基酸序列和生物活性方面具有显着的相似性,但它们的进化起源尚未得到解决。为了研究这个问题,我们最近从原始脊索动物物种文昌鱼(Branchiostoma californiensis)中克隆了编码胰岛素样肽(ILP)的 cDNA。文昌鱼 preproILP 的推导序列表明它是一种混合分子,包含胰岛素和 IGF 的特征。 与胰岛素原一样,文昌鱼 proILP 含有 C 肽,其两侧是成对的碱性残基,可能通过蛋白水解作用去除。然而,proILP 还包含一个扩展的羧基末端肽区域,与 proIGF 类似,该区域可分为 D 和 E 结构域。序列比较表明文昌鱼ILP A和B结构域与人胰岛素和IGF-I和-II的结构域同样同源。基于这些结果和文昌鱼 ILP 基因的外显子-内含子组织,我们推测 IGF 在脊椎动物进化的早期阶段就从祖先的胰岛素型基因中出现。
Although insulin and the insulin-like growth factors (IGFs) share marked similarities in amino acid sequence and biological activity, their evolutionary origins have not been resolved. To investigate this issue, we recently cloned a cDNA encoding an insulin-like peptide (ILP) from a primitive chordate species, amphioxus (Branchiostoma californiensis). The deduced sequence of amphioxus preproILP indicates that it is a hybrid molecule containing features characteristic of both insulin and IGF. Like proinsulin, amphioxus proILP contains a C-peptide, which is flanked by paired basic residues and is probably removed by proteolysis. However, proILP also contains an extended carboxyl-terminal peptide region that can be divided into D and E domains similar to those of proIGF. Sequence comparisons show that the amphioxus ILP A and B domains are equally homologous to those of human insulin and IGF-I and -II. Based on these results and the exon-intron organization of the amphioxus ILP gene, we propose that IGF emerged at a very early stage in vertebrate evolution from an ancestral insulin-type gene.