PROTEASE NEXINS - CELL-SECRETED PROTEINS THAT MEDIATE THE BINDING, INTERNALIZATION, AND DEGRADATION OF REGULATORY SERINE PROTEASES
PROTEASE NEXINS - CELL-SECRETED PROTEINS THAT MEDIATE THE BINDING, INTERNALIZATION, AND DEGRADATION OF REGULATORY SERINE PROTEASES
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DOI：
10.1002/jcp.1041170314
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发表时间：
1983-01-01
影响因子：
5.6
通讯作者：
CUNNINGHAM, DD
中科院分区：
文献类型：
--
作者：
KNAUER, DJ;THOMPSON, JA;CUNNINGHAM, DD
蛋白酶连结蛋白（PN-I，MW apprx. 38，000; PN-II，MW约95，000;和PN-III，MW apprx。31，000）是最近描述的细胞分泌蛋白，其选择性地连接到细胞外环境中的调节性丝氨酸蛋白酶并介导它们的细胞结合、内化和降解。比较蛋白酶连接蛋白的蛋白酶特异性、肝素敏感性和一般作用模式。通过使用[125I]-凝血酶、[125I]-神经生长因子-γ的竞争性结合测定，（125I-NGF-γ）和[125I]-表皮生长因子结合蛋白（125I-EGF-结合蛋白），根据蛋白酶特异性表征连接蛋白，并且确定PN-I连接并介导凝血酶或尿激酶的细胞结合，而PN-II和PN-III优先连接并介导EGF结合蛋白和NGF-γ的细胞结合，分别此外，尽管PN-I与凝血酶连接的能力受到肝素的强烈调节，但PN-II和PN-III基本上不受肝素的影响。每种连接蛋白与它们各自的蛋白酶的连接需要蛋白酶的催化位点丝氨酸，这通过所测试的蛋白酶的二异丙基磷酸（DIP）衍生物不能连接到它们各自的连接蛋白来判断。连接后，连接蛋白：蛋白酶复合物与细胞结合，迅速内化并最终通过莫能菌素敏感的明显溶酶体途径降解，尽管每个连接蛋白：蛋白酶复合物以其自身的特征速率降解。重要的是，蛋白酶连接蛋白提供了人成纤维细胞与所研究的每种丝氨酸蛋白酶相互作用的主要途径。连接蛋白可能是一类独特的细胞分泌蛋白，使细胞能够监测和选择性调节其环境中的特定丝氨酸蛋白酶。
The protease nexins (PN-I, MW .apprx. 38,000; PN-II, MW .apprx. 95,000; and PN-III, MW .apprx. 31,000) are recently described cell-secreted proteins that selectively link to regulatory serine proteases in the extracellular environment and mediate their cellular binding, internalization and degradation. The protease nexins were compared with respect to protease specificity, heparin sensitivity and general mode of action. By competitive binding assays using [125I]-thrombin, [125I]-nerve growth factor-.gamma. (125I-NGF-.gamma.) and [125I]-epidermal growth factor binding protein (125I-EGF-binding protein), the nexins were characterized in terms of protease specificity, and it was determined that PN-I links to and mediates the cellular binding of thrombin or urokinase, whereas PN-II and PN-III preferentially link to and mediate the cellular binding of the EGF binding protein and NGF-.gamma., respectively. In addition, whereas the ability of PN-I to link to thrombin is strongly modulated by heparin, PN-II and PN-III are essentially unaffected by heparin. The linkage of each of the nexins to their respective proteases requires the catalytic site serine of the protease, judged by the inability of diisopropylphospho (DIP) derivatives of the proteases tested to link to their respective nexins. Subsequent to linkage, the nexin:protease complexes are bound to cells, rapidly internalized and ultimately degraded via a monensin-sensitive apparently lysosomal pathway, although each nexin:protease complex is degraded at its own characteristic rate. Importantly, the protease nexins provide the major pathway through which human fibroblasts interact with each of the serine proteases studied. The nexins may be a unique class of cell-secreted proteins that enable cells to monitor and selectively regulate specific serine proteases in their environment.