The low density lipoprotein receptor-related protein mediates the cellular degradation of tissue factor pathway inhibitor.
The low density lipoprotein receptor-related protein mediates the cellular degradation of tissue factor pathway inhibitor.
复制标题
DOI：
10.1073/pnas.91.14.6664
复制
发表时间：
1994-07
影响因子：
11.1
通讯作者：
I. Warshawsky;G. Broze;A. Schwartz
中科院分区：
文献类型：
--
作者：
I. Warshawsky;G. Broze;A. Schwartz
低密度脂蛋白受体相关蛋白/α 2-巨球蛋白受体（LRP）是一种4525个氨基酸的细胞表面糖蛋白，作为几种血浆蛋白的肝内吞受体发挥作用。这些包括α 2-巨球蛋白-蛋白酶复合物、游离纤溶酶原激活剂以及与其抑制剂复合的纤溶酶原激活剂，以及与载脂蛋白E或脂蛋白脂肪酶复合的β-迁移极低密度脂蛋白。在目前的研究中，我们使用人类和大鼠肝癌细胞系，以证明LRP可以介导的组织因子途径抑制剂（TFPI），一个Kunitz型血浆丝氨酸蛋白酶抑制剂，调节组织因子诱导的血液凝固的降解。针对LRP的抗体和LRP相关39-kDa蛋白（一种抑制所有配体结合和/或细胞介导的降解的蛋白质）均可抑制125 I标记的TFPI（125 I-TFPI）的细胞降解超过80%。LRP。使用大鼠肝癌细胞，我们报告说，在4摄氏度，125 I-TFPI结合约2 × 10（6）个网站每个细胞的平衡解离常数约为30 nM。125 I-TFPI与细胞表面的结合不受39-kDa蛋白的抑制。两者合计，我们的研究结果表明，TFPI结合到一个尚未确定的细胞表面分子。结合后，LRP介导TFPI的细胞降解。
The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) is a cell-surface glycoprotein of 4525 amino acids that functions as a hepatic endocytosis receptor for several plasma proteins. These include alpha 2-macroglobulin-protease complexes, free plasminogen activators as well as plasminogen activators complexed with their inhibitors, and beta-migrating very low density lipoproteins complexed with either apolipoprotein E or lipoprotein lipase. In the current study we used human and rat hepatoma cell lines to demonstrate that LRP can mediate the degradation of tissue factor pathway inhibitor (TFPI), a Kunitz-type plasma serine protease inhibitor that regulates tissue factor-induced blood coagulation. The cellular degradation of 125I-labeled TFPI (125I-TFPI) was inhibited more than 80% both by antibodies directed against LRP and by the LRP-associated 39-kDa protein, a protein that inhibits the binding and/or cell-mediated degradation of all ligands by LRP. Using rat hepatoma cells, we report that at 4 degrees C, 125I-TFPI binds to approximately 2 x 10(6) sites per cell with an equilibrium dissociation constant of approximately 30 nM. 125I-TFPI binding to the cell surface is not inhibited by the 39-kDa protein. Taken together, our results suggest that TFPI binds to an as-yet-unidentified cell surface molecule. After binding, LRP mediates the cellular degradation of TFPI.