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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...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2003
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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. |
format | Text |
id | pubmed-2172889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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