Mammals have two insulin-like growth factors (IGF) that are key mediators of somatic growth, tissue differentiation, and cellular responses to stress. Thus, the mechanisms that regulate the bioavailability of IGFs are important in both normal and aberrant development. IGF-I levels are primarily controlled via the growth hormone-IGF axis, in response to nutritional status, and also reflect metabolic diseases and cancer. One mechanism that controls IGF bioavailablity is the binding of circulating IGF to a number of binding proteins that keep IGF in a stable, but receptor non-binding state. However, even before IGF is released from the cells that produce it, it undergoes an obligatory association with a ubiquitous chaperone protein, GRP94. This binding is required for secretion of a properly folded, mature IGF. This chapter reviews the known aspects of the interaction and highlights the specificity issues yet to be determined. The IGF–GRP94 interaction provides a potential novel mechanism of idiopathic short stature, involving the obligatory chaperone and not just IGF gene expression. It also provides a novel target for cancer treatment, as GRP94 activity can be either inhibited or enhanced.

中文翻译：

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葡萄糖调节蛋白94（GRP94）：胰岛素样生长因子生产的新型调节剂。

哺乳动物具有两种胰岛素样生长因子（IGF），它们是体细胞生长，组织分化和细胞对应激反应的关键介质。因此，调节IGFs生物利用度的机制在正常和异常发育中都很重要。响应营养状况，IGF-I水平主要通过生长激素-IGF轴控制，还反映了代谢性疾病和癌症。控制IGF生物利用度的一种机制是循环IGF与许多结合蛋白的结合，这些结合蛋白使IGF保持稳定，但不与受体结合。但是，即使在IGF从产生它的细胞中释放出来之前，它也必须与普遍存在的伴侣蛋白GRP94进行强制性结合。这种结合是分泌正确折叠的成熟IGF所必需的。本章回顾了相互作用的已知方面，并突出了尚未确定的特异性问题。IGF-GRP94相互作用提供了特发性矮小身材的潜在新机制，涉及强制性伴侣，而不仅仅是IGF基因表达。由于GRP94活性可以被抑制或增强，因此它也为癌症治疗提供了新的靶点。