蛋白酶PAPP-A在IGF系统之外有着深刻的进化根源.
Caroline M N Kjeldsen1, Claus Oxvig1
1Department of Molecular Biology and Genetics, Aarhus University, Aarhus DK-8000 C, Denmark.
Genome biology and evolution
|March 14, 2025
概括
包括PAPP-A和PAPP-A2在内的动物帕帕利辛调节了IGF系统. 研究人员发现了一种新的无脊椎动物帕帕素 (invPAPP-A),并发现了保存的功能,这表明其作用超出了IGF结合蛋白的范围.
科学领域:
- 生物化学 生物化学
- 进化生物学 进化生物学
- 酶学 是一种酶学.
背景情况:
- 帕帕利辛 (PAPP-A) 和PAPP-A2是金属蛋白酶,通过分裂IGF结合蛋白 (IGFBPs) 来调节胰岛素样生长因子 (IGF) 系统.
- 斯坦尼奥卡尔辛-1和-2 (STC1/STC2) 抑制了帕帕利辛,形成了STC-PAPP-A-IGFBP-IGF轴.
- 了解pappalysin的演变和功能至关重要,特别是因为PAPP-A是一种新兴的药物标.
研究的目的:
- 为了研究动物王国中pappalysins的进化存在和功能性保护.
- 为了确定新型的pappalysin组及其与已知的脊椎动物形式的关系.
- 探索帕帕利辛在已建立的IGF系统之外的潜在功能.
主要方法:
- 利用同类学搜索和遗传学分析来识别和分类pappalysin酶.
- 检查了超级动物pappalysins中保存的域架构和功能动机.
- 对比了PAPP-A,PAPP-A2和无脊椎动物的pappalysins (invPAPP-A) 的进化起源.
主要成果:
- 帕帕利辛在甲基动物中广泛存在,有三个不同的群体被确定:PAPP-A,PAPP-A2和invPAPP-A.
- PAPP-A和PAPP-A2起源于脊椎动物早期进化中的基因重复.
- 甲基动物的pappalysins共享保存的域架构和功能动机.
- invPAPP-A功能独立于IGFBPs,表明潜在的新基质和角色.
结论:
- 帕帕利辛家族是古老的,在动物中广泛保存,脊椎动物和无脊椎动物的演化轨迹是不同的.
- 保存的功能元素表明了pappalysins的基本作用,而invPAPP-A突出了潜在的未发现功能.
- 对帕帕利辛的非IGFBP基质进行进一步的研究是有必要的,特别是考虑到PAPP-A作为药物标的地位.
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