Role of PDI in regulating tissue factor: FVIIa activity.
Cell exposed tissue factor (TF) is generally in a low procoagulant ("cryptic") state, and requires an activation step (decryption) to exhibit its full procoagulant potential. Recent data suggest that TF decryption may be regulated by the redox environment through the oxidoreductase activity of protein disulfide isomerase (PDI). In this article we review PDI contribution to different models of TF decryption, namely the disulfide switch model and the phosphatidylserine dynamics, and hypothesize on PDI contribution to TF self-association and association with lipid domains. Experimental evidence debate the disulfide switch model of TF decryption and its regulation by PDI. More recently we showed that PDI oxidoreductase activity regulates the phosphatidylserine equilibrium at the plasma membrane. Interestingly, PDI reductase activity could maintain TF in the reduced monomeric form, while also maintaining low exposure of PS, both states correlated with low procoagulant function. In contrast, PDI inhibition or oxidants may promote the adverse effects with a net increase in coagulation. The relative contribution of disulfide isomerization and PS exposure needs to be further analyzed to understand the redox control of TF procoagulant function. For the moment however TF regulation remains cryptic.
Popescu
Narcis I
NI
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Lupu
Cristina
C
Lupu
Florea
F
D000495:Allosteric Site; D001777:Blood Coagulation; D015942:Factor VIIa / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D018832:Molecular Chaperones / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases / Q000737:chemistry*; D013925:Thromboplastin / Q000737:chemistry
D008055:Lipids; D018832:Molecular Chaperones; D016877:Oxidants; D010455:Peptides; D010718:Phosphatidylserines; D013925:Thromboplastin; D010088:Oxidoreductases; D015942:Factor VIIa; D019704:Protein Disulfide-Isomerases