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 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.

• Publication year

  2003

• Venue

  Journal of Cell Biology

• Publication date

  2003-04-14

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/jcb.200208145PMID 12695504PMCID 2172889
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2004cited by this paper
• Transcription: MAPK-regulated transcription: a continuously variable gene switch?

  2002cited by this paper
• Normalizing DNA microarray data.

  2002influential reference
• New functions for the matrix metalloproteinases in cancer progression

  2002cited by this paper
• Frequent co-localization of Cox-2 and laminin-5 gamma2 chain at the invasive front of early-stage lung adenocarcinomas.

  2002cited by this paper
• Signaling through the EGF receptor controls lung morphogenesis in part by regulating MT1-MMP-mediated activation of gelatinase A/MMP2.

  2002cited by this paper
• Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains.

  2002cited by this paper
• The Short Arm of the Laminin γ2 Chain Plays a Pivotal Role in the Incorporation of Laminin 5 into the Extracellular Matrix and in Cell Adhesion

  2001cited by this paper
• Role of basement membrane in tumor growth and metastasis.

  2001influential reference
• Sole Expression of Laminin γhain in Invading Tumor Cells and Its Association with Stromal Fibrosis in Lung Adenocarcinomas

  2001cited by this paper
• MAP kinases.

  2001cited by this paper
• Proteases in invasion: matrix metalloproteinases.

  2001cited by this paper
• Matrix metalloproteinases in cancer invasion, metastasis and angiogenesis.

  2001cited by this paper
• Expression of the gamma(2) chain of laminin-5 at the invasive front is associated with recurrence and poor prognosis in human esophageal squamous cell carcinoma.

  2001cited by this paper
• Contribution of MT1-MMP and of human laminin-5 gamma2 chain degradation to mammary epithelial cell migration.

  2001cited by this paper
• The EGFR family and its ligands in human cancer. signalling mechanisms and therapeutic opportunities.

  2001cited by this paper
• Spontaneous air space enlargement in the lungs of mice lacking tissue inhibitor of metalloproteinases-3 (TIMP-3).

  2001cited by this paper
• Accelerated apoptosis in the Timp-3-deficient mammary gland.

  2001influential reference
• The LG3 Module of Laminin-5 Harbors a Binding Site for Integrin α3β1 That Promotes Cell Adhesion, Spreading, and Migration*

  2001cited by this paper
• Epidermal growth factor (EGF)-like repeats of human tenascin-C as ligands for EGF receptor

  2001influential reference
• Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2, and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma.

  2001cited by this paper
• Expression of the γ2 Chain of Laminin-5 at the Invasive Front Is Associated with Recurrence and Poor Prognosis in Human Esophageal Squamous Cell Carcinoma

  2001cited by this paper
• The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells.

  2001cited by this paper
• A Novel Member of the Netrin Family, β-Netrin, Shares Homology with the β Chain of Laminin

  2000cited by this paper
• Cell signaling by receptor tyrosine kinases.

  2000cited by this paper
• Sustained Down-regulation of the Epidermal Growth Factor Receptor by Decorin

  2000cited by this paper
• Integrins as receptors for laminins

  2000cited by this paper
• Role of Cell Surface Metalloprotease Mt1-Mmp in Epithelial Cell Migration over Laminin-5

  2000cited by this paper
• Dystroglycan inside and out.

  1999cited by this paper
• Expression of matrix metalloprotease-2-cleaved laminin-5 in breast remodeling stimulated by sex steroids.

  1999cited by this paper
• Processing of the notch ligand delta by the metalloprotease Kuzbanian.

  1999cited by this paper
• Laminin-5 promotes adhesion and migration of epithelial cells: identification of a migration-related element in the gamma2 chain gene (LAMC2) with activity in transgenic mice.

  1999cited by this paper
• Quantification of Short Term Signaling by the Epidermal Growth Factor Receptor*

  1999cited by this paper
• Gene expression profiles of laser-captured adjacent neuronal subtypes

  1999cited by this paper
• Structure and function of hemidesmosomes: more than simple adhesion complexes.

  1999cited by this paper
• Role of the plasminogen activator and matrix metalloproteinase systems in epidermal growth factor- and scatter factor-stimulated invasion of carcinoma cells.

  1998cited by this paper
• EGF receptor regulation of cell motility: EGF induces disassembly of focal adhesions independently of the motility-associated PLCgamma signaling pathway.

  1998cited by this paper
• Recombinant soluble human alpha 3 beta 1 integrin: purification, processing, regulation, and specific binding to laminin-5 and invasin in a mutually exclusive manner.

  1998cited by this paper
• Epidermal growth factor (EGF)‐ and scatter factor/hepatocyte growth factor (SF/HGF)‐mediated keratinocyte migration is coincident with induction of matrix metalloproteinase (MMP)‐9

  1998cited by this paper
• Proteinase requirements of epidermal growth factor–induced ovarian cancer cell invasion

  1998cited by this paper
• Epidermal growth factor and amphiregulin up‐regulate matrix metalloproteinase‐9 (MMP‐9) in human breast cancer cells

  1997cited by this paper
• The discoidin domain receptor tyrosine kinases are activated by collagen.

  1997cited by this paper
• Regulation of Cell Motility by Mitogen-activated Protein Kinase

  1997cited by this paper
• Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-beta1 release.

  1997cited by this paper
• Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5.

  1997cited by this paper
• COOH-terminal Extended Recombinant Amphiregulin with Bioactivity Comparable with Naturally Derived Growth Factor*

  1996cited by this paper
• Decorin regulates collagenase gene expression in fibroblasts adhering to vitronectin.

  1996cited by this paper
• Rapid spreading and mature hemidesmosome formation in HaCaT keratinocytes induced by incubation with soluble laminin-5r.

  1995influential reference
• Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord.

  1994cited by this paper
• Domain organizations of extracellular matrix proteins and their evolution

  1994cited by this paper
• The gamma 2 chain of kalinin/laminin 5 is preferentially expressed in invading malignant cells in human cancers.

  1994cited by this paper
• Self-assembly and calcium-binding sites in laminin. A three-arm interaction model.

  1993cited by this paper
• A single EGF‐like motif of laminin is responsible for high affinity nidogen binding.

  1993cited by this paper
• Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution

  1992cited by this paper
• Domains of laminin with growth-factor activity.

  1989cited by this paper
• Regulation of cell attachment and cell number by fibronectin and laminin

  1986cited by this paper
• Laminin increases the release of type IV collagenase from malignant cells.

  1986cited by this paper
• An activated S6 kinase in extracts from serum- and epidermal growth factor-stimulated Swiss 3T3 cells.

  1984cited by this paper

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  2025cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
• [Laminins in Metastatic Cancer].

  2018cites this paper
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  2018cites this paper
• Mechanotransduction pulls the strings of matrix degradation at invadosome.

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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
• Bioactive extracellular matrix fragments in lung health and disease.

  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2015cites this paper
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  2015cites this paper
• FGFR1 mediates recombinant thrombomodulin domain-induced angiogenesis.

  2015cites this paper
• [A novel biomarker for diagnosis of bladder cancer].

  2015cites this paper
• Role of ErbB Receptors in Cancer Cell Migration and Invasion

  2015cites this paper
• Dynamic Reciprocity Between Cells and Their Microenvironment in Reproduction1

  2015influential citation
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper