PAI-1: An Integrator of Cell Signaling and Migration
Cellular migration, over simple surfaces or through complex stromal barriers, requires coordination between detachment/re-adhesion cycles, involving structural components of the extracellular matrix and their surface-binding elements (integrins), and the precise regulation of the pericellular proteo...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2011-01-01
|
| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2011/562481 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832545885442015232 |
|---|---|
| author | Ralf-Peter Czekay Cynthia E. Wilkins-Port Stephen P. Higgins Jennifer Freytag Jessica M. Overstreet R. Matthew Klein Craig E. Higgins Rohan Samarakoon Paul J. Higgins |
| author_facet | Ralf-Peter Czekay Cynthia E. Wilkins-Port Stephen P. Higgins Jennifer Freytag Jessica M. Overstreet R. Matthew Klein Craig E. Higgins Rohan Samarakoon Paul J. Higgins |
| author_sort | Ralf-Peter Czekay |
| collection | DOAJ |
| description | Cellular migration, over simple surfaces or through complex stromal barriers, requires coordination between detachment/re-adhesion cycles, involving structural components of the extracellular matrix and their surface-binding elements (integrins), and the precise regulation of the pericellular proteolytic microenvironment. It is now apparent that several proteases and protease inhibitors, most notably urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1), also interact with several cell surface receptors transducing intracellular signals that significantly affect both motile and proliferative programs. These events appear distinct from the original function of uPA/PAI-1 as modulators of the plasmin-based proteolytic cascade. The multifaceted interactions of PAI-1 with specific matrix components (i.e., vitronectin), the low-density lipoprotein receptor-related protein-1 (LRP1), and the uPA/uPA receptor complex have dramatic consequences on the migratory phenotype and may underlie the pathophysiologic sequalae of PAI-1 deficiency and overexpression. This paper focuses on the increasingly intricate role of PAI-1 as a major mechanistic determinant of the cellular migratory phenotype. |
| format | Article |
| id | doaj-art-dd56c16186b74e539fd175654b06a175 |
| institution | Kabale University |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj-art-dd56c16186b74e539fd175654b06a1752025-02-03T07:24:36ZengWileyInternational Journal of Cell Biology1687-88761687-88842011-01-01201110.1155/2011/562481562481PAI-1: An Integrator of Cell Signaling and MigrationRalf-Peter Czekay0Cynthia E. Wilkins-Port1Stephen P. Higgins2Jennifer Freytag3Jessica M. Overstreet4R. Matthew Klein5Craig E. Higgins6Rohan Samarakoon7Paul J. Higgins8Center for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USACenter for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USACenter for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USACenter for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USACenter for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USACenter for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USACenter for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USACenter for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USACenter for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USACellular migration, over simple surfaces or through complex stromal barriers, requires coordination between detachment/re-adhesion cycles, involving structural components of the extracellular matrix and their surface-binding elements (integrins), and the precise regulation of the pericellular proteolytic microenvironment. It is now apparent that several proteases and protease inhibitors, most notably urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1), also interact with several cell surface receptors transducing intracellular signals that significantly affect both motile and proliferative programs. These events appear distinct from the original function of uPA/PAI-1 as modulators of the plasmin-based proteolytic cascade. The multifaceted interactions of PAI-1 with specific matrix components (i.e., vitronectin), the low-density lipoprotein receptor-related protein-1 (LRP1), and the uPA/uPA receptor complex have dramatic consequences on the migratory phenotype and may underlie the pathophysiologic sequalae of PAI-1 deficiency and overexpression. This paper focuses on the increasingly intricate role of PAI-1 as a major mechanistic determinant of the cellular migratory phenotype.http://dx.doi.org/10.1155/2011/562481 |
| spellingShingle | Ralf-Peter Czekay Cynthia E. Wilkins-Port Stephen P. Higgins Jennifer Freytag Jessica M. Overstreet R. Matthew Klein Craig E. Higgins Rohan Samarakoon Paul J. Higgins PAI-1: An Integrator of Cell Signaling and Migration International Journal of Cell Biology |
| title | PAI-1: An Integrator of Cell Signaling and Migration |
| title_full | PAI-1: An Integrator of Cell Signaling and Migration |
| title_fullStr | PAI-1: An Integrator of Cell Signaling and Migration |
| title_full_unstemmed | PAI-1: An Integrator of Cell Signaling and Migration |
| title_short | PAI-1: An Integrator of Cell Signaling and Migration |
| title_sort | pai 1 an integrator of cell signaling and migration |
| url | http://dx.doi.org/10.1155/2011/562481 |
| work_keys_str_mv | AT ralfpeterczekay pai1anintegratorofcellsignalingandmigration AT cynthiaewilkinsport pai1anintegratorofcellsignalingandmigration AT stephenphiggins pai1anintegratorofcellsignalingandmigration AT jenniferfreytag pai1anintegratorofcellsignalingandmigration AT jessicamoverstreet pai1anintegratorofcellsignalingandmigration AT rmatthewklein pai1anintegratorofcellsignalingandmigration AT craigehiggins pai1anintegratorofcellsignalingandmigration AT rohansamarakoon pai1anintegratorofcellsignalingandmigration AT pauljhiggins pai1anintegratorofcellsignalingandmigration |