Transglutaminases catalyze cross-linking of plasminogen to fibronectin and human endothelial cells.
We have previously reported that apolipoprotein (a) is a substrate for transglutaminases. We now demonstrate that plasminogen which is homologous to apolipoprotein (a), is also modified by these enzymes. Transglutaminases from different sources mediated the incorporation of monodansyl-cadaverine into plasminogen, indicating the presence of reactive glutamine(s) in plasminogen. Reactive lysines were also identified using the lysine-decorating peptide dansyl-PGGQQIV. In addition, transglutaminases catalyzed the formation of plasminogen homopolymers and plasminogen-fibronectin heteropolymers. Human umbilical vein endothelial cells cross-linked plasminogen into high molecular mass aggregates. Cross-linked plasminogen was cell associated, and no cross-linking of plasminogen was seen in the fluid-phase. Large molecular mass plasminogen generated on the human umbilical vein endothelial cell (HUVEC) surface could not be eluted with epsilon-aminocapoic acid and was activatable by tissue plasminogen activator. These results suggest that, following non-covalent association of plasminogen with the HUVEC surface, cell surface-associated transglutaminase catalyzes cross-linking of plasminogen into large molecular mass aggregates that can be converted into functional plasmin. It is proposed that transglutaminases may function to localize plasminogen to cell surfaces and matrices of tissues.
Bendixen
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E
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
Borth
W
W
Harpel
P C
PC
D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D011503:Transglutaminases / Q000378:metabolism*
D003432:Cross-Linking Reagents; D005353:Fibronectins; D009842:Oligopeptides; D010958:Plasminogen; D011503:Transglutaminases