Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors
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Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors. / Ellis, V; Wun, T.-C.; Behrendt, N; Rønne, E; Danø, K.
In: The Journal of Biological Chemistry, Vol. 265, No. 17, 15.06.1990, p. 9904-8.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors
AU - Ellis, V
AU - Wun, T.-C.
AU - Behrendt, N
AU - Rønne, E
AU - Danø, K
PY - 1990/6/15
Y1 - 1990/6/15
N2 - Urokinase-type plasminogen activator (uPA) binds to a specific receptor on various cell types, the bound molecule retaining its enzymatic activity against plasminogen. We have now investigated whether receptor-bound uPA also retains the ability to react with and be inhibited by plasminogen activator inhibitors (PAI-1 and PAI-2). uPA bound to its receptor on human U937 monocyte-like cells was inhibited by PAI-1 (in its active form in the presence of vitronectin fragments) with an association rate constant of 4.5 x 10(6) M-1 s-1, which was 40% lower than that obtained for uPA in solution (7.9 x 10(6) M-1 s-1). The inhibition of uPA by PAI-2 was decreased to a similar extent by receptor binding, falling from 5.3 x 10(5) to 3.3 x 10(5) M-1 s-1. Stimulation of U937 cells with phorbol 12-myristate 13-acetate was accompanied by a further reduction in receptor-bound uPA inhibition by PAI-1 and PAI-2 to 1.7 x 10(6) and 1.1 x 10(5) M-1 s-1, respectively. These constants although lower than those for uPA in solution still represent rather rapid inhibition of the enzyme, and demonstrate that uPA bound to its specific cellular receptor remains available for efficient inhibition by PAI's, which may therefore play a major role in controlling cell-surface plasminogen activation and extracellular proteolytic activity.
AB - Urokinase-type plasminogen activator (uPA) binds to a specific receptor on various cell types, the bound molecule retaining its enzymatic activity against plasminogen. We have now investigated whether receptor-bound uPA also retains the ability to react with and be inhibited by plasminogen activator inhibitors (PAI-1 and PAI-2). uPA bound to its receptor on human U937 monocyte-like cells was inhibited by PAI-1 (in its active form in the presence of vitronectin fragments) with an association rate constant of 4.5 x 10(6) M-1 s-1, which was 40% lower than that obtained for uPA in solution (7.9 x 10(6) M-1 s-1). The inhibition of uPA by PAI-2 was decreased to a similar extent by receptor binding, falling from 5.3 x 10(5) to 3.3 x 10(5) M-1 s-1. Stimulation of U937 cells with phorbol 12-myristate 13-acetate was accompanied by a further reduction in receptor-bound uPA inhibition by PAI-1 and PAI-2 to 1.7 x 10(6) and 1.1 x 10(5) M-1 s-1, respectively. These constants although lower than those for uPA in solution still represent rather rapid inhibition of the enzyme, and demonstrate that uPA bound to its specific cellular receptor remains available for efficient inhibition by PAI's, which may therefore play a major role in controlling cell-surface plasminogen activation and extracellular proteolytic activity.
KW - Antibodies
KW - Antigen-Antibody Complex
KW - Cell Line
KW - Enzyme Precursors
KW - Humans
KW - Kinetics
KW - Plasminogen
KW - Plasminogen Activators
KW - Plasminogen Inactivators
KW - Receptors, Cell Surface
KW - Receptors, Urokinase Plasminogen Activator
KW - Tetradecanoylphorbol Acetate
KW - Tumor Cells, Cultured
KW - Urokinase-Type Plasminogen Activator
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
M3 - Journal article
C2 - 2161846
VL - 265
SP - 9904
EP - 9908
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 17
ER -
ID: 180824241