The role of pro-domains in human growth factors and cytokines.
The role of pro-domains in human growth factors and cytokines.
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DOI：
10.1042/bst20200663
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发表时间：
2021-11-01
影响因子：
3.9
通讯作者：
Hyvönen M
中科院分区：
文献类型：
--
作者：
Ratcliff M;Zhou RX;Jermutus L;Hyvönen M
许多生长因子和细胞因子是作为较大的前体产生的，含有前结构域，需要蛋白水解处理才能释放生物活性配体。这些前结构域可以明显大于成熟结构域，并且可以在配体的调节中发挥积极作用。挖掘UniProt数据库，我们确定了近100个人类生长因子和细胞因子的前域。它们分布在几个不相关的蛋白质家族中，它们的大小和组成各不相同。每个前结构域的确切作用在蛋白质家族之间有显著差异。通常，它们对于控制生物活性和蛋白质定位至关重要，并且它们促进了多种激活机制。我们对前结构域功能的理解仍然存在重大差距-特别是一旦生物活性配体释放后它们的命运。在这里，我们概述了前结构域在人类生长因子和细胞因子中的作用，它们的加工，调节和激活，定位以及治疗潜力。
Many growth factors and cytokines are produced as larger precursors, containing pro-domains, that require proteolytic processing to release the bioactive ligand. These pro-domains can be significantly larger than the mature domains and can play an active role in the regulation of the ligands. Mining the UniProt database, we identified almost one hundred human growth factors and cytokines with pro-domains. These are spread across several unrelated protein families and vary in both their size and composition. The precise role of each pro-domain varies significantly between the protein families. Typically they are critical for controlling bioactivity and protein localisation, and they facilitate diverse mechanisms of activation. Significant gaps in our understanding remain for pro-domain function — particularly their fate once the bioactive ligand has been released. Here we provide an overview of pro-domain roles in human growth factors and cytokines, their processing, regulation and activation, localisation as well as therapeutic potential.