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Insulin-Like Growth Factor Binding Proteins: A Structural Perspective
Insulin-like growth factor binding proteins (IGFBP-1 to -6) bind insulin-like growth factors-I and -II (IGF-I and IGF-II) with high affinity. These binding proteins maintain IGFs in the circulation and direct them to target tissues, where they promote cell growth, proliferation, differentiation, and...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Research Foundation
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356058/ https://www.ncbi.nlm.nih.gov/pubmed/22654863 http://dx.doi.org/10.3389/fendo.2012.00038 |
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author | Forbes, Briony E. McCarthy, Peter Norton, Raymond S. |
author_facet | Forbes, Briony E. McCarthy, Peter Norton, Raymond S. |
author_sort | Forbes, Briony E. |
collection | PubMed |
description | Insulin-like growth factor binding proteins (IGFBP-1 to -6) bind insulin-like growth factors-I and -II (IGF-I and IGF-II) with high affinity. These binding proteins maintain IGFs in the circulation and direct them to target tissues, where they promote cell growth, proliferation, differentiation, and survival via the type 1 IGF receptor. IGFBPs also interact with many other molecules, which not only influence their modulation of IGF action but also mediate IGF-independent activities that regulate processes such as cell migration and apoptosis by modulating gene transcription. IGFBPs-1 to -6 are structurally similar proteins consisting of three distinct domains, N-terminal, linker, and C-terminal. There have been major advances in our understanding of IGFBP structure in the last decade and a half. While there is still no structure of an intact IGFBP, several structures of individual N- and C-domains have been solved. The structure of a complex of N-BP-4:IGF-I:C-BP-4 has also been solved, providing a detailed picture of the structural features of the IGF binding site and the mechanism of binding. Structural studies have also identified features important for interaction with extracellular matrix components and integrins. This review summarizes structural studies reported so far and highlights features important for binding not only IGF but also other partners. We also highlight future directions in which structural studies will add to our knowledge of the role played by the IGFBP family in normal growth and development, as well as in disease. |
format | Online Article Text |
id | pubmed-3356058 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Frontiers Research Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-33560582012-05-31 Insulin-Like Growth Factor Binding Proteins: A Structural Perspective Forbes, Briony E. McCarthy, Peter Norton, Raymond S. Front Endocrinol (Lausanne) Endocrinology Insulin-like growth factor binding proteins (IGFBP-1 to -6) bind insulin-like growth factors-I and -II (IGF-I and IGF-II) with high affinity. These binding proteins maintain IGFs in the circulation and direct them to target tissues, where they promote cell growth, proliferation, differentiation, and survival via the type 1 IGF receptor. IGFBPs also interact with many other molecules, which not only influence their modulation of IGF action but also mediate IGF-independent activities that regulate processes such as cell migration and apoptosis by modulating gene transcription. IGFBPs-1 to -6 are structurally similar proteins consisting of three distinct domains, N-terminal, linker, and C-terminal. There have been major advances in our understanding of IGFBP structure in the last decade and a half. While there is still no structure of an intact IGFBP, several structures of individual N- and C-domains have been solved. The structure of a complex of N-BP-4:IGF-I:C-BP-4 has also been solved, providing a detailed picture of the structural features of the IGF binding site and the mechanism of binding. Structural studies have also identified features important for interaction with extracellular matrix components and integrins. This review summarizes structural studies reported so far and highlights features important for binding not only IGF but also other partners. We also highlight future directions in which structural studies will add to our knowledge of the role played by the IGFBP family in normal growth and development, as well as in disease. Frontiers Research Foundation 2012-03-02 /pmc/articles/PMC3356058/ /pubmed/22654863 http://dx.doi.org/10.3389/fendo.2012.00038 Text en Copyright © 2012 Forbes, McCarthy and Norton. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited. |
spellingShingle | Endocrinology Forbes, Briony E. McCarthy, Peter Norton, Raymond S. Insulin-Like Growth Factor Binding Proteins: A Structural Perspective |
title | Insulin-Like Growth Factor Binding Proteins: A Structural Perspective |
title_full | Insulin-Like Growth Factor Binding Proteins: A Structural Perspective |
title_fullStr | Insulin-Like Growth Factor Binding Proteins: A Structural Perspective |
title_full_unstemmed | Insulin-Like Growth Factor Binding Proteins: A Structural Perspective |
title_short | Insulin-Like Growth Factor Binding Proteins: A Structural Perspective |
title_sort | insulin-like growth factor binding proteins: a structural perspective |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356058/ https://www.ncbi.nlm.nih.gov/pubmed/22654863 http://dx.doi.org/10.3389/fendo.2012.00038 |
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