title: Heterotrimeric G proteins, focal adhesion kinase, and endothelial barrier function.
abstract: Ligands by binding to G protein coupled receptors (GPCRs) stimulate dissociation of heterotrimeric G proteins into Gα and Gβγ subunits. Released Gα and Gβγ subunits induce discrete signaling cues that differentially regulate focal adhesion kinase (FAK) activity and endothelial barrier function. Activation of G proteins downstream of receptors such as protease activated receptor 1 (PAR1) and histamine receptors rapidly increases endothelial permeability which reverses naturally within the following 1-2 h. However, activation of G proteins coupled to the sphingosine-1-phosphate receptor 1 (S1P1) signal cues that enhance basal barrier endothelial function and restore endothelial barrier function following the increase in endothelial permeability by edemagenic agents. Intriguingly, both PAR1 and S1P1 activation stimulates FAK activity, which associates with alteration in endothelial barrier function by these agonists. In this review, we focus on the role of the G protein subunits downstream of PAR1 and S1P1 in regulating FAK activity and endothelial barrier function.
authors.affiliation: Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Thennes
authors.forename: Dolly
authors.initials: D
authors.lastname: Mehta
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D042783:Endothelial Cells / Q000201:enzymology*; D004789:Enzyme Activation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D022001:Focal Adhesions / Q000201:enzymology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D044463:Receptor, PAR-1 / Q000378:metabolism; D011968:Receptors, Histamine / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D044463:Receptor, PAR-1; D011968:Receptors, Histamine; D049349:Receptors, Lysosphingolipid; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020962:Heterotrimeric GTP-Binding Proteins