Bendixen E, Borth W, Harpel P C
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
J Biol Chem. 1993 Oct 15;268(29):21962-7.
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.
我们之前报道过载脂蛋白(a)是转谷氨酰胺酶的底物。我们现在证明，与载脂蛋白(a)同源的纤溶酶原也会被这些酶修饰。来自不同来源的转谷氨酰胺酶介导单丹磺酰尸胺掺入纤溶酶原，表明纤溶酶原中存在反应性谷氨酰胺。还使用赖氨酸修饰肽丹磺酰-PGGQQIV鉴定了反应性赖氨酸。此外，转谷氨酰胺酶催化纤溶酶原同聚物和纤溶酶原-纤连蛋白杂聚物的形成。人脐静脉内皮细胞将纤溶酶原交联成高分子量聚集体。交联的纤溶酶原与细胞相关，在液相中未观察到纤溶酶原的交联。在人脐静脉内皮细胞(HUVEC)表面产生的大分子量纤溶酶原不能用ε-氨基己酸洗脱，并且可被组织纤溶酶原激活剂激活。这些结果表明，在纤溶酶原与HUVEC表面非共价结合后，细胞表面相关的转谷氨酰胺酶催化纤溶酶原交联成可转化为功能性纤溶酶的大分子量聚集体。有人提出，转谷氨酰胺酶可能起到将纤溶酶原定位到组织的细胞表面和基质的作用。
