RESUMEN
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.
Asunto(s)
Adhesión Celular/fisiología , Comunicación Celular/fisiología , Células Epiteliales , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Proteínas de Unión al GTP rho/metabolismo , Animales , Biomarcadores/metabolismo , Línea Celular , Forma de la Célula , Células Epiteliales/citología , Células Epiteliales/fisiología , Proteína-Tirosina Quinasas de Adhesión Focal/genética , Humanos , Fosforilación , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Ratas , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Proteínas de Unión al GTP rac/genética , Proteínas de Unión al GTP rac/metabolismo , Proteínas de Unión al GTP rho/genéticaRESUMEN
Recent studies using animal models have demonstrated an important role for FAK in the cardiovascular system. In particular, FAK is essential for angiogenesis in the embryo, functions in heart development and modulates the response of cardiomyocytes to pressure overload in adult mice. FAK function at the cellular level is discussed to provide insight into the mechanisms regulating these biological events and the role of FAK in controlling endothelial junctions and responses to mechanical stimulation are discussed.