The integrin α5β1 regulates αvβ3-mediated extracellular signal-regulated kinase activation

Daphne P. Ly, Siobhan A. Corbett

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Integrin-mediated cell migration is essential for wound repair. Previous studies have shown that the interaction between integrins and the extracellular matrix (ECM) can initiate intracellular signaling pathways to regulate cell movement. Both the focal adhesion kinase (FAK) and the extracellular signal-regulated kinase/activated mitogen-activated protein kinase (ERK/MAPK) signaling pathways are required for efficient cell migration. Our previous work has shown that co-expression of the integrin α5β1 inhibits αvβ3-mediated cell migration. We hypothesized that α5β1 may regulate cell migration by modulating these αvβ3-mediated intracellular signaling events. CHO B3 (αvβ3+) and B3C5 (αvβ3+/α5β1+) cells were monitored by flow cytometry to determine integrin expression. Cells were allowed to migrate on fibrinogen (FBG)-coated transwells, with or without PD98059, an inhibitor of the ERK activator, mitogen-activated protein kinase kinase (MEK). Fixation, staining, and cell counting were used to quantify cell migration. Cells adherent to FBG were lysed and analyzed for FAK and ERK/MAPK activation by immunoblotting followed by image analysis densitometry. All experiments were repeated in triplicate. Treatment with PD98059 significantly decreased αvβ3-mediated cell migration on FBG (P = 0.0001) to a level comparable to untreated B3C5 cells. Following adhesion to FBG, B3 cells demonstrated a marked increase in ERK/MAPK activation compared to B3C5 cells. However, no significant difference was detected in FAK activation. Signaling through the ERK/MAPK pathway is required for efficient αvβ3-mediated migration on FBG. Inhibition of αvβ3-mediated migration by the integrin α5β1 correlates with altered intensity and duration of ERK/MAPK activation, but not FAK activation, in response to adhesion. This suggests a mechanism for the regulatory effect of α5β1 on αvβ3-mediated cell migration.

Original languageEnglish (US)
Pages (from-to)200-205
Number of pages6
JournalJournal of Surgical Research
Volume123
Issue number2
DOIs
StatePublished - Feb 2005

All Science Journal Classification (ASJC) codes

  • Surgery

Keywords

  • ERK activation
  • cell migration
  • cell signaling
  • fibronectin
  • integrins

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