The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein

The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein
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DOI:
10.1074/jbc.m102727200
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发表时间:
2001-08-03
影响因子:
4.8
通讯作者:
Bu, GJ
Bu, GJ
中科院分区:
生物学2区
文献类型:
--
作者:
Liu, CX;Li, YH;Bu, GJ

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低密度脂蛋白受体相关蛋白。LRP 1B(LRP-DIT)是一种肿瘤抑制基因。是低密度脂蛋白受体基因家族的新成员。其整体结构域结构和大尺寸(类似于600 kDa)与LRP相似,表明它是一种多功能细胞表面受体。在这里,我们的特点是一系列的配体的受体使用细胞系,稳定表达它作为一个域IV微受体(mLRP 1B 4)。LRP的配体包括受体相关蛋白、尿激酶型纤溶酶原激活物、组织型纤溶酶原激活物和纤溶酶原激活物抑制剂1型。底物结合,内化和降解通过mLRP 1B 4。有趣的是,配体内吞作用的动力学与LRP明显不同,LRP 1B表现出明显降低的内化率。此外,组织表达分析显示LRP 1B基因在脑、甲状腺和唾液腺中表达。因此,这些研究扩展了LDL受体家族成员的生理作用。
The low density lipoprotein receptor-related protein. deleted in tumor (LRP1B, initially referred to as LRP-DIT) was cloned and characterized as a candidate tumor suppressor. It is a new member of the low density lipoprotein receptor gene family. Its overall domain structure and large size (similar to 600 kDa) are similar to LRP and suggest that it is a multifunctional cell surface receptor. Herein, we characterize a series of ligands for the receptor using cell lines that stably express it as a domain IV minireceptor (mLRP1B4). Ligands of LRP including receptor-associated protein, urokinase plasminogen activator, tissue-type plasminogen activator, and plasminogen activator inhibitor type-1 each demon. strate binding, internalization, and degradation via mLRP1B4. Interestingly, the kinetics of ligand endocytosis is distinctly different from that of LRP, with LRP1B exhibiting a markedly diminished internalization rate. In addition, tissue expression analysis reveals that the LRP1B gene is expressed in brain, thyroid, and salivary gland. These studies thus extend the physiological roles of members of the LDL receptor family.