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

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

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 an...

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Main Authors: Andrew J. Blyth, Nicholas S. Kirk, Briony E. Forbes
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Cells
Subjects:
IGF-II
insulin-like growth factor
IGF-1R
insulin receptor
IR-A
structural studies
Online Access:https://www.mdpi.com/2073-4409/9/10/2276
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spelling doaj-9afca672a603486094d802138c0389dd2020-11-25T03:53:56ZengMDPI AGCells2073-44092020-10-0192276227610.3390/cells9102276Understanding IGF-II Action through Insights into Receptor Binding and ActivationAndrew J. Blyth0Nicholas S. Kirk1Briony E. Forbes2Department of Medical Biochemistry, Flinders Health and Medical Research Institute, Flinders University, Bedford Park 5042, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, AustraliaDepartment of Medical Biochemistry, Flinders Health and Medical Research Institute, Flinders University, Bedford Park 5042, AustraliaThe 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.https://www.mdpi.com/2073-4409/9/10/2276IGF-IIinsulin-like growth factorIGF-1Rinsulin receptorIR-Astructural studies
collection DOAJ
language English
format Article
sources DOAJ
author Andrew J. Blyth
Nicholas S. Kirk
Briony E. Forbes
spellingShingle Andrew J. Blyth
Nicholas S. Kirk
Briony E. Forbes
Understanding IGF-II Action through Insights into Receptor Binding and Activation
Cells
IGF-II
insulin-like growth factor
IGF-1R
insulin receptor
IR-A
structural studies
author_facet Andrew J. Blyth
Nicholas S. Kirk
Briony E. Forbes
author_sort Andrew J. Blyth
title Understanding IGF-II Action through Insights into Receptor Binding and Activation
title_short Understanding IGF-II Action through Insights into Receptor Binding and Activation
title_full Understanding IGF-II Action through Insights into Receptor Binding and Activation
title_fullStr Understanding IGF-II Action through Insights into Receptor Binding and Activation
title_full_unstemmed Understanding IGF-II Action through Insights into Receptor Binding and Activation
title_sort understanding igf-ii action through insights into receptor binding and activation
publisher MDPI AG
series Cells
issn 2073-4409
publishDate 2020-10-01
description 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.
topic IGF-II
insulin-like growth factor
IGF-1R
insulin receptor
IR-A
structural studies
url https://www.mdpi.com/2073-4409/9/10/2276
work_keys_str_mv AT andrewjblyth understandingigfiiactionthroughinsightsintoreceptorbindingandactivation
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AT brionyeforbes understandingigfiiactionthroughinsightsintoreceptorbindingandactivation
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