A role for the thiol isomerase protein ERP5 in platelet function.

نویسندگان

  • Peter A Jordan
  • Joanne M Stevens
  • Gary P Hubbard
  • Natasha E Barrett
  • Tanya Sage
  • Kalwant S Authi
  • Jonathan M Gibbins
چکیده

Formation and rearrangement of disulfide bonds during the correct folding of nascent proteins is modulated by a family of enzymes known as thiol isomerases, which include protein disulfide isomerase (PDI), endoplasmic reticulum protein 5 (ERP5), and ERP57. Recent evidence supports an alternative role for this family of proteins on the surface of cells, where they are involved in receptor remodeling and recognition. In platelets, blocking PDI with inhibitory antibodies inhibits a number of platelet activation pathways, including aggregation, secretion, and fibrinogen binding. Analysis of human platelet membrane fractions identified the presence of the thiol isomerase protein ERP5. Further study showed that ERP5 is resident mainly on platelet intracellular membranes, although it is rapidly recruited to the cell surface in response to a range of platelet agonists. Blocking cell-surface ERP5 using inhibitory antibodies leads to a decrease in platelet aggregation in response to agonists, and a decrease in fibrinogen binding and P-selectin exposure. It is possible that this is based on the disruption of integrin function, as we observed that ERP5 becomes physically associated with the integrin beta(3) subunit during platelet stimulation. These results provide new insights into the involvement of thiol isomerases and regulation of platelet activation.

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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A role for the thiol isomerase protein ERP5 in platelet function

Formation and rearrangement of disulfide bonds during the correct folding of nascent proteins is modulated by a family of enzymes known as thiol isomerases, which include protein disulfide isomerase (PDI), endoplasmic reticulum protein 5 (ERP5), and ERP57. Recent evidence supports an alternative role for this family of proteins on the surface of cells, where they are involved in receptor remode...

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The platelet-surface thiol isomerase enzyme ERp57 modulates platelet function

BACKGROUND Thiol isomerases are a family of endoplasmic reticulum enzymes which orchestrate redox-based modifications of protein disulphide bonds. Previous studies have identified important roles for the thiol isomerases PDI and ERp5 in the regulation of normal platelet function. AIM Recently, we demonstrated the presence of a further five thiol isomerases at the platelet surface. In this rep...

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عنوان ژورنال:
  • Blood

دوره 105 4  شماره 

صفحات  -

تاریخ انتشار 2005