Andreasen P A, Sottrup-Jensen L, Kjøller L, Nykjaer A, Moestrup S K, Petersen C M, Gliemann J
Department of Molecular Biology, University of Aarhus, Denmark.
FEBS Lett. 1994 Feb 7;338(3):239-45. doi: 10.1016/0014-5793(94)80276-9.
Recent findings have elucidated the mechanism for clearance from the extracellular space of the two types of plasminogen activators, urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA), and their type-1 inhibitor (PAI-1). Activator/PAI-1 complexes and uncomplexed t-PA bind to the multi-ligand receptors alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR) and epithelial glycoprotein 330 (gp330). These receptors mediate endocytosis and degradation of u-PA/PAI-1 complex bound to the glycosyl phosphatidyl inositol-anchored urokinase receptor (u-PAR) on cell surfaces, and participate, in cooperation with other receptors, in hepatic clearance of activator/PAI-1 complexes and uncomplexed t-PA from blood plasma. The alpha 2MR- and gp330-mediated endocytosis of a ligand (u-PA/PAI-1 complex) initially bound to another receptor (u-PAR) is a novel kind of interaction between membrane receptors. Binding to alpha 2MR and gp330 is a novel kind of molecular recognition of serine proteinases and serpins.
最近的研究结果阐明了两种纤溶酶原激活剂，即尿激酶型纤溶酶原激活剂（u-PA）和组织型纤溶酶原激活剂（t-PA）及其1型抑制剂（PAI-1）从细胞外间隙清除的机制。激活剂/PAI-1复合物和未复合的t-PA与多配体受体α2-巨球蛋白受体/低密度脂蛋白受体相关蛋白（α2MR）和上皮糖蛋白330（gp330）结合。这些受体介导与细胞表面糖基磷脂酰肌醇锚定的尿激酶受体（u-PAR）结合的u-PA/PAI-1复合物的内吞作用和降解，并与其他受体协同参与从血浆中清除激活剂/PAI-1复合物和未复合的t-PA的肝脏清除过程。α2MR和gp330介导的最初与另一种受体（u-PAR）结合的配体（u-PA/PAI-1复合物）的内吞作用是膜受体之间一种新型的相互作用。与α2MR和gp330的结合是丝氨酸蛋白酶和丝氨酸蛋白酶抑制剂的一种新型分子识别。
