Purified alpha 2-macroglobulin receptor/LDL receptor-related protein binds urokinase.plasminogen activator inhibitor type-1 complex. Evidence that the alpha 2-macroglobulin receptor mediates cellular degradation of urokinase receptor-bound complexes.
Purified alpha 2-macroglobulin receptor/LDL receptor-related protein binds urokinase.plasminogen activator inhibitor type-1 complex. Evidence that the alpha 2-macroglobulin receptor mediates cellular degradation of urokinase receptor-bound complexes.
复制标题
DOI：
10.1016/s0021-9258(18)42072-8
复制
发表时间：
1992-07
期刊：
影响因子：
--
通讯作者：
Anders NykjaerSO;Claus M. Petersenl;Bjarne Mdllerl;Poul H. JensenS;MoestrupS;Thor L. Holtetll;Michael EtzerodtJI;Hans C. ThdgersenJJ;M. Munch;P. Andreasen;Jdrgen GliemannSO
中科院分区：
文献类型：
--
作者：
Anders NykjaerSO;Claus M. Petersenl;Bjarne Mdllerl;Poul H. JensenS;MoestrupS;Thor L. Holtetll;Michael EtzerodtJI;Hans C. ThdgersenJJ;M. Munch;P. Andreasen;Jdrgen GliemannSO
125 I标记的尿激酶型纤溶酶原激活剂（uPA）和1型纤溶酶原激活剂抑制剂（派-1）之间的复合物与纯化的α 2-巨球蛋白（α 2 M）受体（α 2 MR）/低密度脂蛋白受体相关蛋白（LRP）结合。使用uPA时未观察到结合。uPA、派-1的结合强度与α 2 MR相关蛋白（α 2 MRAP）的结合强度相当。派-1的结合被天然和重组α 2 MRAP阻断，并且约80%被组织型纤溶酶原激活物（tPA）和派-1之间的复合物以及被单克隆抗PAI-1抗体抑制。在人单核细胞中，uPA、派-1与uPA及其氨基端片段一样，与尿激酶受体（uPAR）结合。与uPAR结合的125 I-uPA.派-1的降解比未结合uPAR的uPA增强3-4倍。ralpha 2 MRAP可阻断UPA降解，而多克隆抗-alpha 2 MR/LRP抗体可抑制UPA降解。这被认为是α 2 MR/LRP介导uPAR结合的uPA·派-1的内化和降解的证据。
Complexes between 125I-labeled urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) bound to purified alpha 2-macroglobulin (alpha 2M) receptor (alpha 2MR)/low density lipoprotein receptor-related protein (LRP). No binding was observed when using uPA. The magnitude of uPA.PAI-1 binding was comparable with that of the alpha 2MR-associated protein (alpha 2MRAP). Binding of uPA.PAI-1 was blocked by natural and recombinant alpha 2MRAP, and about 80% inhibited by complexes between tissue-type plasminogen activator (tPA) and PAI-1, and by a monoclonal anti-PAI-1 antibody. In human monocytes, uPA.PAI-1, like uPA and its amino-terminal fragment, bound to the urokinase receptor (uPAR). Degradation of uPAR-bound 125I-uPA.PAI-1 was 3-4-fold enhanced as compared with uncomplexed uPAR-bound uPA. The inhibitor-enhanced uPA degradation was blocked by r alpha 2MRAP and inhibited by polyclonal anti-alpha 2MR/LRP antibodies. This is taken as evidence for mediation of internalization and degradation of uPAR-bound uPA.PAI-1 by alpha 2MR/LRP.