Kinetics and mechanism of platelet-surface plasminogen activation by tissue-type plasminogen activator

Biochemistry. 1994 Mar 15;33(10):2970-6. doi: 10.1021/bi00176a029.

Abstract

Plasminogen and tissue-type plasminogen activator bind to the platelet surface, and as a result, the catalytic efficiency of plasminogen activation is significantly enhanced. The plasmin that is generated on or near the platelet is known to affect a number of platelet surface events. For this reason, we examined the effect of plasmin on platelet-surface plasminogen activation and its determinants. Specifically, we measured the effects of plasmin treatment of platelets (1 caseinolytic unit/mL for 1 h at 37 degrees C) on plasminogen, tissue-type plasminogen activator, and plasmin binding to the unactivated and ADP-activated platelet surface; and on the kinetics of plasminogen activation on the platelet surface. Following plasmin treatment, the number of plasminogen binding sites on unactivated platelets increased by 78% (from 46,000 +/- 4000 to 88,000 +/- 9000 sites/platelet), while the number of tissue-type plasminogen activator sites did not change, and the number of diisopropyl fluorophosphate (DFP)-inactivated plasmin (DFP-plasmin) binding sites decreased by 31% (from 92,000 +/- 11,000 to 65,000 +/- 7000 sites/platelet); the dissociation constants (Kds) for each of these binding processes did not change significantly following treatment. On ADP-activated platelets, plasmin treatment increased the number of plasminogen binding sites by 41% (from 188,000 +/- 17,000 to 265,000 +/- 25,000 sites/platelet), decreased the number of plasmin binding sites by 28% (from 219,000 +/- 41,000 to 157,000 +/- 24,000 sites/platelet), and did not affect the number of tissue-type plasminogen activator sites; again, the Kds for each of these binding processes did not change significantly following treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding, Competitive
  • Blood Platelets / cytology
  • Blood Platelets / metabolism*
  • Cell Membrane / metabolism
  • Cell Separation
  • Chromatography, Gel
  • Fibrinolysin / metabolism
  • Humans
  • Kinetics
  • Mathematics
  • Models, Theoretical*
  • Plasminogen / metabolism*
  • Receptors, Cell Surface / metabolism
  • Receptors, Urokinase Plasminogen Activator
  • Tissue Plasminogen Activator / metabolism*

Substances

  • PLAUR protein, human
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Plasminogen
  • Tissue Plasminogen Activator
  • Fibrinolysin