Understanding IGF-II Action through Insights into Receptor Binding and Activation.

Andrew J Blyth, Nicholas S Kirk, Briony E Forbes

Cells 2020 Oct 12

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The insulin-like growth factor (IGF) system regulates metabolic and mitogenic signaling through an intricate network of related receptors and hormones. IGF-II is one of several hormones within this system that primarily regulates mitogenic functions and is especially important during fetal growth and development. IGF-II is also found to be overexpressed in several cancer types, promoting growth and survival. It is also unique in the IGF system as it acts through both IGF-1R and insulin receptor isoform A (IR-A). Despite this, IGF-II is the least investigated ligand of the IGF system. This review will explore recent developments in IGF-II research including a structure of IGF-II bound to IGF-1R determined using cryo-electron microscopy (cryoEM). Comparisons are made with the structures of insulin and IGF-I bound to their cognate receptors. Finally discussed are outstanding questions in the mechanism of action of IGF-II with the goal of developing antagonists of IGF action in cancer.

Citation

Andrew J Blyth, Nicholas S Kirk, Briony E Forbes. Understanding IGF-II Action through Insights into Receptor Binding and Activation. Cells. 2020 Oct 12;9(10)