Rho GTPases and leukocyte adhesion receptor expression and function in endothelial cells.
Rho family GTPases are key signal transducers that regulate cell adhesion and migration and a variety of other cellular responses, including changes in gene expression. In this review, we discuss how Rho GTPases regulate signaling by endothelial cell receptors involved in leukocyte extravasation. First, Rho GTPases affect the expression of some leukocyte adhesion molecules on endothelial cells, such as intracellular adhesion molecule-1 and E-selectin, that can be induced by proinflammatory mediators, hypoxia, or shear stress. Second, Rho GTPases are activated by engagement of several leukocyte adhesion receptors and contribute to both early morphological changes and subsequent alterations in gene expression. Rho GTPases are therefore candidate targets for inhibiting leukocyte transendothelial migration in heart disease and chronic inflammatory disorders.
Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, London, UK.
Eva
E
Cernuda-Morollón
Anne J
AJ
Ridley
D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology*; D002450:Cell Communication; D002465:Cell Movement; D019040:E-Selectin / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D039041:Integrin alpha4beta1 / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007962:Leukocytes / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D019007:P-Selectin / Q000502:physiology; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D015398:Signal Transduction; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology*
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; D019007:P-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D020741:rho GTP-Binding Proteins