Protein disulphide isomerase in platelet function.
Platelet protein disulphide isomerase (PDI) has a role in platelet aggregation, probably targeting a thiol-containing platelet surface protein. The thiol-containing P2Y(12) ADP receptor is involved in aggregation induced by most agonists and may be the target of PDI. By excluding the P2Y(12) pathway and using the anti-PDI antibody RL90 this study showed that PDI targets a non-P2Y(12) thiol-protein in aggregation. Anti-PDI inhibited signalling-independent activation of the thiol-containing fibrinogen receptor alphaIIbbeta3 by Mn(2+), suggesting that PDI directly interacts with alphaIIbbeta3. The thiol-containing form of PDI increased on the platelet surface with platelet activation, suggesting that active PDI readily becomes available for redox regulation of alphaIIbbeta3. Finally, using purified proteins PDI had greater ability to isomerize disulphide bonds than the alphaIIbbeta3 integrin, which also has PDI-like activity. In summary, a mechanism exists in platelets to increase the functional form of surface PDI and this PDI has a non-P2Y(12) target that may be alphaIIbbeta3.
Manickam
Nagaraj
N
Division of Hematology, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Sun
Xiuhua
X
Li
Mengru
M
Gazitt
Yair
Y
Essex
David W
DW
D000911:Antibodies, Monoclonal / Q000276:immunology; D001792:Blood Platelets / Q000201:enzymology / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D015636:Magnesium Chloride / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D012260:Ribonucleases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D000911:Antibodies, Monoclonal; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D015636:Magnesium Chloride; D012260:Ribonucleases; D019704:Protein Disulfide-Isomerases