Interplay between FAK, PKCδ, and p190RhoGAP in the regulation of endothelial barrier function

Disruption of either intercellular or extracellular junctions involved in maintaining endothelial barrier function can result in increased endothelial permeability. Increased endothelial permeability, in turn, allows for the unregulated movement of fluid and solutes out of the vasculature and into the surrounding connective tissue, contributing to a number of disease states, including stroke and pulmonary edema (Ermert et al., 1995, Lee and Slutsky, 2010, van Hinsbergh, 1997, Waller et al., 1996 and Warboys et al., 2010). Thus, a better understanding of the molecular mechanisms by which endothelial cell junction integrity is controlled is necessary for development of therapies aimed at treating such conditions. In this review, we will discuss the functions of three signaling molecules known to be involved in regulation of endothelial permeability: focal adhesion kinase (FAK), protein kinase C delta (PKCδ), and p190RhoGAP (p190). We will discuss the independent functions of each protein, as well as the interplay that exists between them and the effects of such interactions on endothelial function.

Research highlights
► FAK, PKC, and p190RhoGAP exhibit crosstalk in their regulation of endothelial cell (EC) function.
► Changes in PKCδ correlate with alterations in FAK activity and related effects on EC function.
► FAK inhibition decreases p190RhoGAP activation; whereas PKCδ inihibition increases p190RhoGAP activation.
► PKCδ and p190RhoGAP may regulate FAK differentially in settings of barrier maintenance versus recovery.