JCB logo
BD Biosciences
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 14 April 2003. doi:10.1083/jcb.200208145
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 795K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schenk, S.
Right arrow Articles by Quaranta, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schenk, S.
Right arrow Articles by Quaranta, V.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0021-9525/2003/4/197 $5.00
The Journal of Cell Biology, Volume 161, Number 1, 197-209

Article

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

Susann Schenk1, Edith Hintermann1, Martin Bilban1, Naohiko Koshikawa1, Carlo Hojilla2, Rama Khokha2 and Vito Quaranta1

1 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037
2 Ontario Cancer Institute/University Health Network, University of Toronto, Toronto, Ontario, Canada M5G 2M9

Address correspondence to Susann Schenk, The Scripps Research Institute, 10550 North Torrey Pines Road, Mail-Drop VB-1, La Jolla, CA 92037. Tel.: (858) 784-7191. Fax: (858) 784-7333. E-mail: sschenk{at}scripps.edu; or Vito Quaranta, The Scripps Research Institute, 10550 North Torrey Pines Road, Mail-Drop SBR-12, La Jolla, CA 92037. Tel.: (858) 784-2907. Fax: (858) 784-2246. E-mail: quaranta{at}scripps.edu

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.

Key Words: ECM; MMP-2 gene expression; microarray; receptor tyrosine kinase; TIMP-3 knockout mouse

* Abbreviations used in this paper: AR, amphiregulin; BM, basement membrane; EGFR, epidermal growth factor receptor; ERK, extracellular signal–regulated kinase; LE, laminin-type EGF; Ln-1, laminin-1; Ln-5, laminin-5; MMP, matrix metalloproteinase; rDIII, recombinant DIII; RTK, receptor tyrosine kinase; TIMP-3, tissue inhibitor of metalloproteinase 3; WT, wild-type.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents