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Examining the Dynamics of Cellular Adhesion and Spreading of Epithelial Cells on Fibronectin During Oxidative Stress
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Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover

X D Ren1, W B Kiosses, D J Sieg

  • 1Departments of Vascular Biology and Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.

Journal of Cell Science
|October 6, 2000
PubMed

Insights

Focal adhesion kinase (FAK) regulates cell migration by controlling Rho activity. Loss of FAK leads to persistent Rho activation, hindering focal adhesion turnover and causing migration defects.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Focal adhesion kinase (FAK) plays a crucial role in cell adhesion and migration.
  • FAK is activated at focal adhesions upon binding to extracellular matrices.
  • The small GTPase Rho regulates cell migration and focal adhesion dynamics.

Purpose of the Study:

  • To investigate the role of FAK in regulating Rho activity.
  • To understand the mechanism by which FAK influences cell migration.
  • To elucidate the cause of embryonic lethality in FAK knockout mice.

Main Methods:

  • Analysis of FAK-deficient (FAK-/-) mouse fibroblasts.
  • Assessment of Rho activity upon plating on fibronectin.
  • Evaluation of focal adhesion turnover.
  • Re-expression of FAK in FAK-/- cells.

Main Results:

  • FAK-/- fibroblasts exhibited a failure to transiently inhibit Rho activity.
  • Re-expression of FAK restored normal Rho regulation.
  • Focal adhesion turnover was inversely correlated with Rho activity.
  • Inhibiting or activating Rho mimicked the presence or absence of FAK, respectively.

Conclusions:

  • Loss of FAK leads to constitutive Rho activation.
  • Constitutive Rho activation inhibits focal adhesion turnover.
  • These FAK-dependent Rho dysregulations account for impaired cell migration and embryonic lethality in FAK knockout models.

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