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Processing of integrin αv subunit by membrane type 1 matrix metalloproteinase stimulates migration of breast carcinoma cells on vitronectin and enhances tyrosine phosphorylation of focal adhesion kinase

Academic Article
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Overview

authors

  • Deryugina, Elena
  • Ratnikov, B. I.
  • Postnova, T. I.
  • Rozanov, D. V.
  • Strongin, A. Y.

publication date

  • 2002

journal

  • Journal of Biological Chemistry  Journal

abstract

  • Recently, we have shown that membrane type 1 matrix metalloproteinase (MT1-MMP) exhibits integrin convertase activity. Similar to furin-like proprotein convertases, MT1-MMP directly processes a single chain precursor of alpha(v) integrin subunit (pro-alpha(v)) into the heavy and light alpha-chains connected by a disulfide bridge. To evaluate functionality of MT1-MMP-processed integrins, we examined breast carcinoma MCF7 cells co-expressing alpha(v)beta(3) integrin with either the wild type or mutant MT1-MMP in a variety of migration and adhesion tests. Specific inhibitors of proprotein convertases and MMP were employed in our cell system to attenuate the individual pathways of pro-alpha(v) maturation. We present evidence that MT1-MMP cleavage of pro-alpha(v) in the cells did not affect RGD-ligand binding of the resulting alpha(v)beta(3) integrin but enhanced outside-in signal transduction through a focal adhesion kinase pathway. Enhanced tyrosine phosphorylation of focal adhesion kinase in cells co-expressing MT1-MMP and alpha(v)beta(3) integrin contributed to efficient adhesion and, especially, migration of cells on vitronectin, a ligand of alpha(v)beta(3) integrin. These mechanisms underscore the significance of a coordinated interplay between MT1-MMP and alpha(v)beta(3) integrin in tumor cells and identify downstream signaling pathways resulting from their interactions. Regulation of integrin maturation and functionality may be an important role of MT1-MMP in tumor cells.

subject areas

  • Antineoplastic Agents
  • Binding Sites
  • Blotting, Western
  • Cell Adhesion
  • Cell Movement
  • Disulfides
  • Dose-Response Relationship, Drug
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Humans
  • Ligands
  • Matrix Metalloproteinase 1
  • Oligopeptides
  • Organic Chemicals
  • Phosphorylation
  • Precipitin Tests
  • Protein Binding
  • Protein-Tyrosine Kinases
  • Receptors, Vitronectin
  • Time Factors
  • Transfection
  • Tumor Cells, Cultured
  • Tyrosine
  • Vitronectin
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Identity

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M110269200

PubMed ID

  • 11724803
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Additional Document Info

start page

  • 9749

end page

  • 9756

volume

  • 277

issue

  • 12

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