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Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution

Extracellular matrix (ECM) fragments or cryptic sites unmasked by proteinases have been postulated to affect tissue remodeling and cancer progression. Therefore, the elucidation of their identities and functions is of great interest. Here, we show that matrix metalloproteinases (MMPs) generate a dom...

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Detalles Bibliográficos
Autores principales: Schenk, Susann, Hintermann, Edith, Bilban, Martin, Koshikawa, Naohiko, Hojilla, Carlo, Khokha, Rama, Quaranta, Vito
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172889/
https://www.ncbi.nlm.nih.gov/pubmed/12695504
http://dx.doi.org/10.1083/jcb.200208145
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author Schenk, Susann
Hintermann, Edith
Bilban, Martin
Koshikawa, Naohiko
Hojilla, Carlo
Khokha, Rama
Quaranta, Vito
author_facet Schenk, Susann
Hintermann, Edith
Bilban, Martin
Koshikawa, Naohiko
Hojilla, Carlo
Khokha, Rama
Quaranta, Vito
author_sort Schenk, Susann
collection PubMed
description Extracellular matrix (ECM) fragments or cryptic sites unmasked by proteinases have been postulated to affect tissue remodeling and cancer progression. Therefore, the elucidation of their identities and functions is of great interest. Here, we show that matrix metalloproteinases (MMPs) generate a domain (DIII) from the ECM macromolecule laminin-5. Binding of a recombinant DIII fragment to epidermal growth factor receptor stimulates downstream signaling (mitogen-activated protein kinase), MMP-2 gene expression, and cell migration. Appearance of this cryptic ECM ligand in remodeling mammary gland coincides with MMP-mediated involution in wild-type mice, but not in tissue inhibitor of metalloproteinase 3 (TIMP-3)–deficient mice, supporting physiological regulation of DIII liberation. These findings indicate that ECM cues may operate via direct stimulation of receptor tyrosine kinases in tissue remodeling, and possibly cancer invasion.
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spelling pubmed-21728892008-05-01 Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution Schenk, Susann Hintermann, Edith Bilban, Martin Koshikawa, Naohiko Hojilla, Carlo Khokha, Rama Quaranta, Vito J Cell Biol Article Extracellular matrix (ECM) fragments or cryptic sites unmasked by proteinases have been postulated to affect tissue remodeling and cancer progression. Therefore, the elucidation of their identities and functions is of great interest. Here, we show that matrix metalloproteinases (MMPs) generate a domain (DIII) from the ECM macromolecule laminin-5. Binding of a recombinant DIII fragment to epidermal growth factor receptor stimulates downstream signaling (mitogen-activated protein kinase), MMP-2 gene expression, and cell migration. Appearance of this cryptic ECM ligand in remodeling mammary gland coincides with MMP-mediated involution in wild-type mice, but not in tissue inhibitor of metalloproteinase 3 (TIMP-3)–deficient mice, supporting physiological regulation of DIII liberation. These findings indicate that ECM cues may operate via direct stimulation of receptor tyrosine kinases in tissue remodeling, and possibly cancer invasion. The Rockefeller University Press 2003-04-14 /pmc/articles/PMC2172889/ /pubmed/12695504 http://dx.doi.org/10.1083/jcb.200208145 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Schenk, Susann
Hintermann, Edith
Bilban, Martin
Koshikawa, Naohiko
Hojilla, Carlo
Khokha, Rama
Quaranta, Vito
Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution
title Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution
title_full Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution
title_fullStr Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution
title_full_unstemmed Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution
title_short Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution
title_sort binding to egf receptor of a laminin-5 egf-like fragment liberated during mmp-dependent mammary gland involution
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172889/
https://www.ncbi.nlm.nih.gov/pubmed/12695504
http://dx.doi.org/10.1083/jcb.200208145
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