IGF-Binding Proteins: Why Do They Exist and Why Are There So Many?
IGF-Binding Proteins: Why Do They Exist and Why Are There So Many?
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DOI：
10.3389/fendo.2018.00117
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发表时间：
2018
影响因子：
5.2
通讯作者：
Duan C
中科院分区：
文献类型：
--
作者：
Allard JB;Duan C
胰岛素样生长因子（IGFs）是促进生长的关键肽，既是内分泌激素，也是自分泌/旁分泌生长因子。在血液和局部组织中，大多数IGF分子与IGF结合蛋白（IGFBP）家族的一种成员结合，其中存在六种不同的类型。这些蛋白以与IGF1受体相同或更高的亲和力与IGF结合，因此在全局和局部调节IGF信号传导方面处于关键位置。与IGFBP结合可增加IGF在循环中的半衰期，并阻断其与胰岛素受体的潜在结合。除了这些经典的作用，igfbp已被证明在各种条件下局部调节IGF信号。虽然IGFBP家族成员具有显著的序列同源性，但它们各自具有独特的结构特征，发挥不同的作用。这些IGFBP基因也具有不同的调控模式和不同的表达模式。一些igfbp已被发现与它们自身的受体结合或转移到细胞的内部区室，在那里它们可能执行与igf无关的作用。尽管存在这种功能和调控的多样性，但令人困惑的是，关于igfbp生理功能的功能丧失研究相对较少。在这篇综述中，我们认为进化倾向于保留一系列igfbp，以促进IGF信号的微调。我们探索了一种新兴的解释，即许多IGFBP功能已经进化到允许在应激或不规则条件下对IGF信号进行有针对性的调节，这在标准实验室环境中可能无法揭示。
Insulin-like growth factors (IGFs) are key growth-promoting peptides that act as both endocrine hormones and autocrine/paracrine growth factors. In the bloodstream and in local tissues, most IGF molecules are bound by one of the members of the IGF-binding protein (IGFBP) family, of which six distinct types exist. These proteins bind to IGF with an equal or greater affinity than the IGF1 receptor and are thus in a key position to regulate IGF signaling globally and locally. Binding to an IGFBP increases the half-life of IGF in the circulation and blocks its potential binding to the insulin receptor. In addition to these classical roles, IGFBPs have been shown to modulate IGF signaling locally under various conditions. Although members of the IGFBP family share significant sequence homology, they each have unique structural features and play distinct roles. These IGFBP genes also have different modes of regulation and distinct expression patterns. Some IGFBPs have been found to bind to their own receptors or to translocate into the interior compartments of cells where they may execute IGF-independent actions. In spite of this functional and regulatory diversity, it has been puzzling that loss-of-function studies have yielded relatively little information about the physiological functions of IGFBPs. In this review, we suggest that evolution has tended to retain an array of IGFBPs in order to facilitate fine-tuning of IGF signaling. We explore the emerging explanation that many IGFBP functions have evolved to allow the targeted adjustment of IGF signaling under stressful or irregular conditions, which would likely not be revealed in a standard laboratory setting.
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DOI：
10.1530/joe-11-0240
发表时间：
2011-12
期刊：
The Journal of endocrinology
影响因子：
--
作者：
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通讯作者：
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影响因子：
6.5
作者：
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影响因子：
4.8
作者：
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通讯作者：
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DOI：
10.1073/pnas.86.18.6898
发表时间：
1989-09-01
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
4.5
作者：
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