title: Vascular thiol isomerases.
abstract: Thiol isomerases are multifunctional enzymes that influence protein structure via their oxidoreductase, isomerase, and chaperone activities. These enzymes localize at high concentrations in the endoplasmic reticulum of all eukaryotic cells where they serve an essential function in folding nascent proteins. However, thiol isomerases can escape endoplasmic retention and be secreted and localized on plasma membranes. Several thiol isomerases including protein disulfide isomerase, ERp57, and ERp5 are secreted by and localize to the membranes of platelets and endothelial cells. These vascular thiol isomerases are released following vessel injury and participate in thrombus formation. Although most of the activities of vascular thiol isomerases that contribute to thrombus formation are yet to be defined at the molecular level, allosteric disulfide bonds that are modified by thiol isomerases have been described in substrates such as αIIbβ3, αvβ3, GPIbα, tissue factor, and thrombospondin. Vascular thiol isomerases also act as redox sensors. They respond to the local redox environment and influence S-nitrosylation of surface proteins on platelets and endothelial cells. Despite our rudimentary understanding of the mechanisms by which thiol isomerases control vascular function, the clinical utility of targeting them in thrombotic disorders is already being explored in clinical trials.
authors.affiliation: Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Robert
authors.initials: R
authors.lastname: Flaumenhaft
authors.affiliation: Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Furie
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000201:enzymology* / Q000473:pathology; D006487:Hemostasis; D006801:Humans; D008954:Models, Biological; D010084:Oxidation-Reduction; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D013927:Thrombosis / Q000201:enzymology / Q000473:pathology
chemical_list: D019704:Protein Disulfide-Isomerases