Interaction of plasminogen and fibrin in plasminogen activation.
Glu1-, Lys77-, miniplasminogens, kringle 1-3, kringle 1-5A, and kringle 1-5R were able to bind with fibrin, while microplasminogen and kringle 4 did not bind significantly. Kringle 1-5A, but not kringle 1-3, effectively inhibited the binding of Glu1-, Lys77-, and miniplasminogens with fibrin. Miniplasminogen also inhibited the binding of Glu1-plasminogen with fibrin. The binding of kringle 1-3 with fibrin was blocked by mini- or Glu1-plasminogen. It is therefore evident that there are two fibrin-binding domains in plasminogen and that the one in kringle 5 is of higher affinity than that in kringle 1-3. CNBr cleavage products of fibrinogen effectively enhanced the activation of Glu1-, Lys77-, or miniplasminogens, but not microplasminogen, by tissue-type plasminogen activator. Kringle 1-5, but not kringle 1-3, dose-dependently inhibited the enhancement by fibrinogen degradation products of Glu1-plasminogen activation by the activator. Lysine and epsilon-aminocaproic acid could inhibit the binding of plasminogens and plasminogen derivatives with fibrin and block the enhancement effect of fibrinogen degradation products on plasminogen activation. The data clearly illustrate that the binding of plasminogen with fibrin, mainly determined by kringle 5, is essential for effective activation by tissue-type plasminogen activator. However, the presence of kringle 1-4 in the plasminogen molecule is required for the full enhancing effect since the kcat/Km of miniplasminogen activation in the presence of fibrinogen degradation products was 8.2 microM-1 min-1 which is significantly less than 52.0 microM-1 min-1 of Glu1-plasminogen.
Wu
H L
HL
Biochemistry Department, Medical College, National Cheng-Kung University, Tainan, Taiwan Republic of China.
Chang
B I
BI
Wu
D H
DH
Chang
L C
LC
Gong
C C
CC
Lou
K L
KL
Shi
G Y
GY
D015119:Aminocaproic Acid / Q000494:pharmacology; D005337:Fibrin / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000494:pharmacology; D008970:Molecular Weight; D010446:Peptide Fragments / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C018998:lysyl-plasminogen; C044190:miniplasminogen; D005337:Fibrin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D008239:Lysine; D015119:Aminocaproic Acid