title: Interplay between FAK, PKCδ, and p190RhoGAP in the regulation of endothelial barrier function.
abstract: 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; 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.
authors.affiliation: Vascular Research Laboratory, Providence VA Medical Center, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI 02908, USA.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Grinnell
authors.forename: Elizabeth O
authors.initials: EO
authors.lastname: Harrington
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D042783:Endothelial Cells / Q000201:enzymology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D022001:Focal Adhesions / Q000201:enzymology*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D051745:Protein Kinase C-delta / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051745:Protein Kinase C-delta