A comparison between activated protein C and des-1-41-light chain-activated protein C in reactions with type 1 plasminogen activator inhibitor.
This study investigates the role of the gamma-carboxyglutamic acid (gla) containing domain of activated protein C in interactions with both platelet-derived and purified type 1 plasminogen activator inhibitor (PAI-1). The activity of human platelet PAI-1 was neutralized to the same extent by bovine activated protein C and bovine des-1-41-light chain-activated protein C. Both forms of activated protein C formed SDS-stable, divalent-cation independent complexes with platelet PAI-1, as demonstrated by immunoblotting using antibodies directed to either protein C or PAI-1. Since activated protein C neutralized PAI-1, the potential inhibition of the enzyme by PAI-1 was studied. Purified PAI-1 inhibited the amidolytic activity of bovine-activated protein C and bovine des-1-41-light chain-activated protein C with a k2 of 2.85 X 10(4) M-1 sec-1 for both proteins. These data suggest that the gla domain of activated protein C is not required for neutralization of PAI-1 activity, for complex formation with PAI-1, or for inhibition of the amidolytic activity of activated protein C by PAI-1.
Gladson
C L
CL
Research Institute of Scripps Clinic, Department of Immunology, La Jolla, CA 92037.
Schleef
R R
RR
Binder
B R
BR
Loskutoff
D J
DJ
Griffin
J H
JH
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D015153:Blotting, Western; D002417:Cattle; D004789:Enzyme Activation; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008970:Molecular Weight; D015849:Plasminogen Inactivators; D011480:Protease Inhibitors / Q000378:metabolism; D011485:Protein Binding; D011486:Protein C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship
D006023:Glycoproteins; D046911:Macromolecular Substances; D015849:Plasminogen Inactivators; D011480:Protease Inhibitors; D011486:Protein C