A comparison between activated protein C and des-1-41-light chain-
activated protein C in reactions with type 1 plasminogen activator
inhibitor
CL Gladson, RR Schleef, BR Binder, DJ Loskutoff and JH Griffin
Research Institute of Scripps Clinic, Department of Immunology, La Jolla,
CA 92037.
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.
Volume 74,
Issue 1,
pp. 173-181,
07/01/1989
Copyright © 1989 by The American Society of Hematology
