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Processing of integrin alpha(v) subunit by membrane type 1 matrix metalloproteinase stimulates migration of breast carcinoma cells on vitronectin and enhances tyrosine phosphorylation of focal adhesion kinase.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2002 Mar 22; Vol. 277 (12), pp. 9749-56. Date of Electronic Publication: 2001 Nov 27. - Publication Year :
- 2002
-
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.
- Subjects :
- Antineoplastic Agents pharmacology
Binding Sites
Blotting, Western
Cell Adhesion
Cell Movement
Disulfides
Dose-Response Relationship, Drug
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Humans
Ligands
Oligopeptides chemistry
Phosphorylation
Precipitin Tests
Protein Binding
Time Factors
Transfection
Tumor Cells, Cultured
Tyrosine chemistry
Matrix Metalloproteinase 1 metabolism
Organic Chemicals
Protein-Tyrosine Kinases metabolism
Receptors, Vitronectin chemistry
Receptors, Vitronectin metabolism
Tyrosine metabolism
Vitronectin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 277
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 11724803
- Full Text :
- https://doi.org/10.1074/jbc.M110269200