title: Disulfide Bonds as Regulators of Integrin Function in Thrombosis and Hemostasis.
abstract: CONCLUSIONS
  Disulfide bonds are generally viewed as structure-stabilizing elements in proteins, but some display an alternative functional role as redox switches. Functional disulfide bonds have recently emerged as important regulators of integrin function in thrombosis and hemostasis.
  
  
  BACKGROUND
  Functional disulfide bonds were identified in the β subunit of the major platelet integrin αIIbβ3 and in other integrins involved in thrombus formation that is, αvβ3 and α2β1. Most of these functional bonds are located in the four epidermal growth factor-like domains of the integrins. Redox agents such as glutathione and nitric oxide and enzymatic thiol isomerase activity were shown to regulate the function of these integrins by disulfide bond reduction and thiol/disulfide exchange.
  
  
  RESULTS
  Increasing evidence suggests that thiol isomerases such as protein disulfide isomerase (PDI) and Erp57 directly bind to the β3 subunit of αIIbβ3 and αvβ3 and regulate their function during thrombus formation. αIIbβ3 also exhibits an endogenous thiol isomerase activity. The specific functional disulfide bonds identified in the β3 subunit might be the targets for both exogenous and endogenous thiol isomerase activity.
  
  
  CONCLUSIONS
  Targeting redox sites of integrins or redox agents and enzymes that regulate their function can provide a useful tool for development of anti-thrombotic therapy. Hence, inhibitors of PDI are currently studied for this purpose.
authors.affiliation: 1 The Amalia Biron Research Institute of Thrombosis and Hemostasis, Chaim Sheba Medical Center , Tel Hashomer, Israel .|2 Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .
authors.forename: Ronit
authors.initials: R
authors.lastname: Mor-Cohen
mesh_terms: D000818:Animals; D005978:Glutathione / Q000378:metabolism; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D013927:Thrombosis / Q000378:metabolism*
chemical_list: D016023:Integrins; D009569:Nitric Oxide; D005978:Glutathione