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

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

doi:10.3390/cells9102276

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

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

Research output: Contribution to journal › Review article › peer-review

37 Citations (Scopus)

41 Downloads (Pure)

Abstract

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 language	English
Article number	2276
Number of pages	13
Journal	Cells
Volume	9
Issue number	10
DOIs	https://doi.org/10.3390/cells9102276
Publication status	Published - Oct 2020
Externally published	Yes

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cells9102276Licence: CC BY

Published versionFinal published version, 2.92 MBLicence: CC BY

Cite this

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title = "Understanding IGF-II Action through Insights into Receptor Binding and Activation",

abstract = "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.",

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author = "Blyth, {Andrew J.} and Kirk, {Nicholas S.} and Forbes, {Briony E.}",

year = "2020",

month = oct,

doi = "10.3390/cells9102276",

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volume = "9",

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T1 - Understanding IGF-II Action through Insights into Receptor Binding and Activation

AU - Blyth, Andrew J.

AU - Kirk, Nicholas S.

AU - Forbes, Briony E.

PY - 2020/10

Y1 - 2020/10

N2 - 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.

AB - 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.

KW - IGF-1R

KW - IGF-II

KW - insulin receptor

KW - insulin-like growth factor

KW - IR-A

KW - receptor activation

KW - structural studies

UR - http://www.scopus.com/inward/record.url?scp=85092886602&partnerID=8YFLogxK

U2 - 10.3390/cells9102276

DO - 10.3390/cells9102276

M3 - Review article

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AN - SCOPUS:85092886602

SN - 2073-4409

VL - 9

JO - Cells

JF - Cells

IS - 10

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ER -

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

Abstract

Keywords

UN SDGs

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