title: Role of FAK in S1P-regulated endothelial permeability.
abstract: The vascular endothelium serves as a semi-selective barrier between the circulating contents of the blood and the tissues through which they flow. Disruption of this barrier results in significant organ dysfunction during devastating inflammatory syndromes such as sepsis and acute lung injury (ALI). Sphingosine 1-phosphate (S1P) is an endogenous lipid regulator of endothelial permeability that produces potent barrier enhancement via actin and junctional protein rearrangement and resultant cytoskeletal changes. A key effector protein in this S1P response is focal adhesion kinase (FAK), a highly conserved cytoplasmic tyrosine kinase involved in the engagement of integrins and assembly of focal adhesions (FA) through the catalysis of multiple downstream signals. After stimulation by S1P, endothelial FAK undergoes specific tyrosine phosphorylation that results in activation of the kinase and dynamic interactions with other effector molecules to improve the endothelial barrier. FAK participates in peripheral actin cytoskeletal rearrangement as well as cell-matrix (FA) and cell-cell (adherens junction) junctional complex strengthening that combine to decrease vascular permeability. This review summarizes the current knowledge of the role of FAK in mediating enhanced endothelial barrier function by S1P.
authors.affiliation: Institute for Personalized Respiratory Medicine, Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Belvitch
authors.forename: Steven M
authors.initials: SM
authors.lastname: Dudek
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*; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D051416:Focal Adhesion Protein-Tyrosine Kinases; D013110:Sphingosine