A form of protease nexin I is expressed on the platelet surface during platelet activation.
A protein that has several similarities to protease nexin I, a fibroblast thrombin and urokinase inhibitor, has been detected on platelets (Gronke RS, Bergman BL, and Baker JB: J Biol Chem 262:3030, 1987). On incubation of platelets with 125I-thrombin, this platelet protein forms complexes with 125I-thrombin that are found both in the incubation medium and, as demonstrated here, associated with purified platelet plasma membranes. The present results indicate that interaction with the platelet surface may modulate the conformation and function of this platelet form of protease nexin I (PNIp) because: (a) an antibody against protease nexin I inhibited released PNIp, but not platelet-bound PNIp from complexing 125I-thrombin, and (b) whereas PNIp extracted from platelets bound both thrombin and urokinase, platelet-bound PNIp bound only thrombin. In experiments using several different platelet isolation methods, PNIp accounted for a large fraction of the rapid high affinity binding of 125I-thrombin to platelets. However, platelets isolated and maintained in the presence of metabolic inhibitors failed to take added thrombin into 125I-thrombin-PNIp complexes. This finding suggests that PNIp is released from inside platelets during activation, and thus does not function to transmit the primary activating signal that is generated by thrombin binding to platelets.
Gronke
R S
RS
Department of Biochemistry, University of Kansas, Lawrence.
Knauer
D J
DJ
Veeraraghavan
S
S
Baker
J B
JB
D016564:Amyloid beta-Protein Precursor; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002352:Carrier Proteins / Q000097:blood*; D003594:Cytoplasmic Granules / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D008565:Membrane Proteins; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D013917:Thrombin; D014568:Urokinase-Type Plasminogen Activator