The Activation of Type 1 and Type 2 Plasminogen by Type I and Type II Tissue Plasminogen Activator (*)

Tissue plasminogen activator (tPA) was fractionated using lysine-Sepharose affinity chromatography. Type I, type II, and a minor peak with high affinity for lysine (designated type D) tPA were recovered. In an indirect amidolytic assay involving native human Glu-plasminogen and fibrin, type II tPA showed a 2-fold higher activity than type I. To explore the combinatorial effect of the variable glycosylation status of both tPA and plasminogen, kinetic constants for fibrin-dependent plasminogen activation were determined for combinations of type I, II, and D tPA with type 1 and 2 plasminogen. Within a 4-fold range, the fastest rate was achieved from the combination of type D* (type II + D) tPA and type 2 plasminogen. N-Glycosylation of plasminogen increased the K value for activation by all tPA variants; N-glycosylation of type I tPA at Asn decreased the k (turnover) values for the fibrin-dependent activation of plasminogen over type II tPA, while type D* tPA showed the highest turnover rate. In the presence of fibrinogen fragments, N-glycosylation of plasminogen at site 289 modulates the kinetics of association of enzyme and substrate, while N-glycosylation at site 184 on tPA modulates the turnover rate of the enzyme.

• Publication year

  1995

• Venue

  Journal of Biological Chemistry

• Publication date

  1995-02-17

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.270.7.3261PMID 7852411
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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