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

Andrew J. Blyth, Nicholas S. Kirk, Briony E. Forbes

Research output: Contribution to journalReview articlepeer-review

30 Citations (Scopus)
29 Downloads (Pure)


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.

Original languageEnglish
Article number2276
Number of pages13
Issue number10
Publication statusPublished - Oct 2020
Externally publishedYes


  • IGF-1R
  • IGF-II
  • insulin receptor
  • insulin-like growth factor
  • IR-A
  • receptor activation
  • structural studies


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