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Involvement of finger domain and kringle 2 domain of tissue‐type plasminogen activator in fibrin binding and stimulation of activity by fibrin.
Author(s) -
Verheijen J.H.,
Caspers M.P.,
Chang G.T.,
Munk G.A.,
Pouwels P.H.,
EngerValk B.E.
Publication year - 1986
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1986.tb04678.x
Subject(s) - fibrin , biology , kringle domain , plasminogen activator , stimulation , fibrinolysis , tissue plasminogen activator , microbiology and biotechnology , t plasminogen activator , biochemistry , plasmin , immunology , endocrinology , medicine , enzyme
Human tissue‐type plasminogen activator (t‐PA) catalyses the conversion of inactive plasminogen into active plasmin, the main fibrinolytic enzyme. This process is confined to the fibrin surface by specific binding of t‐PA to fibrin and stimulation of its activity by fibrin. Tissue‐type plasminogen activator contains five domains designated finger, growth factor, kringle 1, kringle 2 and protease. The involvement of the domains in fibrin specificity was investigated with a set of variant proteins lacking one or more domains. Variant proteins were produced by expression in Chinese hamster ovary cells of plasmids containing part of the coding sequence for the activator. It was found that kringle 2 domain only is involved in stimulation of activity by fibrin. In the absence of plasminogen and at low concentration of fibrin, binding of t‐PA is mainly due to the finger domain, while at high fibrin concentrations also kringle 2 is involved in fibrin binding. In the presence of plasminogen, fibrin binding of the kringle 2 region of t‐PA also becomes important at low fibrin concentrations.