Focal Adhesion Kinase regulates cell-cell contact formation in epithelial cells via modulation of Rho

Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase that plays a key role in cellular processes Such as cell adhesion, migration, proliferation and Survival. Recent studies have also implicated FAK in the regulation of cell-cell adhesion. Here, evidence is presented showing that siRNA-mediated Suppression of FAK levels in NBT-II cells and expression of dominant negative Mutants of FAK caused loss of epithelial cell morphology and inhibited the formation of cell-cell adhesions. Rac and Rho have been implicated in the regulation of cell-cell adhesions and can be regulated by FAK signaling. Expression of active Rac or Rho in NBT-II cells disrupted formation of cell-cell Contacts, thus promoting a phenotype similar to FAK-depleted cells. The loss of intercellular Contacts in FAK-depleted cells is prevented upon expression of a dominant negative Rho mutant, but not a dominant negative Rac mutant. Inhibition of FAK decreased tyrosine phosphorylation of p190RhoGAP and elevated the level of GTP-bound Rho. This Suggests that FAK regulates cell-cell contact formation by regulation of Rho. (C) 2008 Elsevier Inc. All rights reserved.