Role of tyrosine kinase signaling in endothelial cell barrier regulation.
Phosphorylation of proteins on tyrosine acts as a reversible and specific trigger mechanism, forming or disrupting regulatory connections between proteins. Tyrosine kinases and phosphatases participate in multiple cellular processes, and considerable evidence now supports a role for tyrosine phosphorylation in vascular permeability. A semipermeable barrier between the vascular compartment and the interstitium is maintained by the integrity of endothelial monolayer, controlling movement of fluids, macromolecules and leucocytes. Barrier function is regulated by the adjustment of paracellular gaps between endothelial cells (ECs) by two antagonistic forces, centripetal cytoskeletal tension and opposing cell-cell and cell-matrix adhesion forces. Both cytoskeletal filaments and adhesion sites are intimately linked in complex machinery which is regulated by multiple signaling events including protein phosphorylation and/or protein translocation to specific intracellular positions. Tyrosine kinases occupy key positions in the mechanism controlling cell responses mediated through various cell surface receptors, which use tyrosine phosphorylation to transduce extracellular signal.
Johns Hopkins Asthma and Allergy Center, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins, Bayview Circle, Baltimore, MD 21224-6801, USA.
Natalia V
NV
Bogatcheva
Joe G N
JG
Garcia
Alexander D
AD
Verin
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D015815:Cell Adhesion Molecules; D011505:Protein-Tyrosine Kinases