TYPE-2 PLASMINOGEN-ACTIVATOR INHIBITOR IS A SUBSTRATE FOR TROPHOBLAST TRANSGLUTAMINASE AND FACTOR-XIII(A) - TRANSGLUTAMINASE-CATALYZED CROSS-LINKING TO CELLULAR AND EXTRACELLULAR STRUCTURES
TYPE-2 PLASMINOGEN-ACTIVATOR INHIBITOR IS A SUBSTRATE FOR TROPHOBLAST TRANSGLUTAMINASE AND FACTOR-XIII(A) - TRANSGLUTAMINASE-CATALYZED CROSS-LINKING TO CELLULAR AND EXTRACELLULAR STRUCTURES
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DOI：
10.1111/j.1432-1033.1993.tb17906.x
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发表时间：
1993-05-15
期刊：
影响因子：
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通讯作者：
GLIEMANN, J
中科院分区：
文献类型：
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作者：
JENSEN, PH;LORAND, L;GLIEMANN, J
2 型纤溶酶原激活剂抑制剂 (PAI-2) 是一种丝氨酸蛋白酶抑制剂，通过阻断尿激酶和组织型纤溶酶原激活剂来抑制纤维蛋白溶解。 43-kDa PAI-2 分子是某些细胞类型中丰富的胞质蛋白，但在适当的刺激下可以分泌为大约 60-70-kDa 的糖蛋白。然而，在滋养层膜中，PAI-2 活性与大的共价复合物相关（Jensen, P. H.、Nykjaer, P.、Andreasen P. A.、Lund, L.、Astedt, B. Lecander, 1. & Gliemann, J. (1989) Biochim. Biophys. Acta 986, 135-140)。这项研究表明，PAI-2 可以作为组织转谷氨酰胺酶和活化血浆因子 XIII 的底物。在 Ca2+ 存在的情况下，这些物质中的任何一个都会催化伯胺（例如腐胺）掺入 PAI-2。此外，在与组织转谷氨酰胺酶的反应中，观察到PAI-2均聚物以及与其他生物底物结合的杂聚物。通过将I-125-尿激酶掺入到耐SDS的I-125-尿激酶/PAI-2复合物中的测试判断，聚合的PAI-2保留了其抑制活性。此外，合体滋养层微绒毛膜和滋养层洗涤剂提取物在腐胺和转谷氨酰胺酶合成抑制剂抑制的反应中将 I-125-PAI-2 掺入大型结构中。通过非变性凝胶电泳和丹酰尸胺活性染色、纤连蛋白结合和用特异性抗体进行蛋白质印迹，将滋养层转谷氨酰胺酶鉴定为组织转谷氨酰胺酶。 PAI-2 转谷氨酰胺酶催化和 Ca2+ 依赖性锚定到细胞外膜结构可能具有局部调节纤维蛋白溶解的目的。
Plasminogen-activator inhibitor type-2 (PAI-2), a serine-proteinase inhibitor, suppresses fibrinolysis by blocking both urokinase and tissue-type plasminogen activators. The 43-kDa PAI-2 molecule is an abundant cytosolic protein in certain cell types, but can upon appropriate stimulation be secreted as an approximately 60-70-kDa glycoprotein. However, in trophoblast membranes PAI-2 activity is associated with large covalent complexes (Jensen, P. H., Nykjaer, P., Andreasen P. A., Lund, L., Astedt, B. Lecander, 1. & Gliemann, J. (1989) Biochim. Biophys. Acta 986, 135-140). This study shows that PAI-2 can act as a substrate for both tissue transglutaminase and activated plasma factor XIII. In the presence of Ca2+, either of these will catalyze the incorporation of primary amines, such as putrescine, into PAI-2. Moreover, in reactions with tissue transglutaminase, PAI-2 homopolymers and, in conjunction with other biological substrates, heteropolymers were observed. As judged by the test of incorporating I-125-urokinase into SDS-resistant I-125-urokinase/PAI-2 complexes, polymerized PAI-2 retained its inhibitory activity. Furthermore, syncytiotrophoblast microvillous membranes and trophoblast detergent extracts incorporated I-125-PAI-2 into large structures in a reaction inhibited by putrescine and a synthetic inhibitor of transglutaminase. Trophoblast transglutaminase was identified as a tissue transglutaminase by non-denaturing gel electrophoresis and dansylcadaverine activity staining, fibronectin binding and Western blotting with a specific antibody. The transglutaminase-catalyzed and Ca2+-dependent anchoring of PAI-2 to extracellular membrane structures might have the purpose of focally regulating fibrinolysis.