Abstract
Tissue and plasma transglutaminases cross-link human plasminogen into high molecular weight complexes (Bendixen, E., Borth, W., and Harpel, P. C. (1993) J. Biol. Chem. 268, 21962-21967). A major cross-linking site in plasminogen involved in the tissue transglutaminase-mediated polymerization process has been identified. The epsilon-(gamma-glutamyl)lysyl bridges of the polymer are formed between Lys-298 and Gln-322. Both the acyl donor Gln residue and the acyl acceptor Lys residue are located in the kringle 3 domain of plasminogen, i.e. cross-linking of plasminogen by tissue transglutaminase involves neither the catalytic domain nor the lysine-dependent binding sites of plasminogen. This study documents that kringle 3 contains a novel functional site with the potential to participate in transglutaminase-mediated cross-linking interactions with plasma, cell-surface, and extracellular proteins.
Highlights
From the Wepartment of Molecular Biology, University of Aarhus, DK-8000 Arhus C, Denmark and the §Division of Hematology, Mount Sinai Medical Center, New York, New York 10029
It has become a basic concept that the interaction of plasminogen with protein matrices and cell surfaces plays a key role in the regulation of plasminogen activation, so plasmin activity is restricted to sites where its proteolytic activity is
It has previously been suggested that plasminogen cross-linked into high molecular weight homopolymers may be cross-linked to the extracellular matrix as well and that this cross-linking of plasminogen may represent a novel mechanism by which plasmin activity is targeted to the extracellular matrix of vascular tissues (Bendixen et al, 1993)
Summary
From the Wepartment of Molecular Biology, University of Aarhus, DK-8000 Arhus C, Denmark and the §Division of Hematology, Mount Sinai Medical Center, New York, New York 10029. The E·(y-glutamyl)lysyl bridges of the polymer are formed between Lys-298 and Gln-322 Both the acyl donor Gin residue and the acyl acceptor Lys residue are located in the kringle 3 domain of plasminogen, i.e. cross-linking of plasminogen by tissue transglutaminase involves neither the catalytic domain nor the lysine-dependent binding sites of plasminogen. We have recently found that plasminogen is a substrate for transglutaminases from plasma as well as tissues These enzymes cross-link plasminogen into high molecular weight homopolymers and cross-link plasminogen to fibronectin, a major constituent of the extracellular matrix of vascular tissues (Bendixen et al, 1993). It has previously been suggested that plasminogen cross-linked into high molecular weight homopolymers may be cross-linked to the extracellular matrix as well and that this cross-linking of plasminogen may represent a novel mechanism by which plasmin activity is targeted to the extracellular matrix of vascular tissues (Bendixen et al, 1993)
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