Characterization of GPR56 protein and its suppressed expression in human pancreatic cancer cells
Characterization of GPR56 protein and its suppressed expression in human pancreatic cancer cells
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DOI：
10.1007/s11010-007-9621-4
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发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Zhu, Guo-Zhang
中科院分区：
文献类型：
--
作者：
Huang, Yue;Fan, Jun;Zhu, Guo-Zhang
GPR56 是一种非典型 G 蛋白偶联受体 (GPCR)，具有异常大的 N 端胞外区域，其中包含长的富含 Ser/Thr 的区域，形成粘蛋白样茎，由于这一特征，GPR56 被认为是粘附 GPCR。最近的研究表明 GPR56 在大脑发育和肿瘤发生中发挥作用。在这里，我们报告人类 GPR56 经历 GPS（GPCR 蛋白水解位点）介导的蛋白质裂解，生成其胞外结构域作为 N 末端片段 (GPR56-N)。我们还表明 GPR56-N 被 N 连接的碳水化合物链高度糖基化。小鼠 Gpr56 在多种组织中广泛表达，其中在肾脏和胰腺中表达量较高。 GPR56 mRNA 在多种人类癌细胞中检测到，包括胰腺癌细胞 PANC-1、Capan-1 和 MiaCaPa-2。有趣的是，尽管观察到高水平的 GPR56 mRNA，但在这些胰腺癌细胞中 GPR56 蛋白可以忽略不计或检测不到。此外，我们发现当用蛋白酶体抑制剂 MG132 处理细胞时，胰腺癌细胞中 GPR56 的蛋白水平没有受到影响。总而言之，这些结果定义了 GPR56 蛋白的生化特性，并表明 GPR56 蛋白的表达在人胰腺癌细胞中受到抑制。
GPR56 is an atypical G protein-coupled receptor (GPCR) with an unusually large N-terminal extracellular region, which contains a long Ser/Thr-rich region forming a mucin-like stalk and due to this feature, GPR56 is thought to be an adhesion GPCR. Recent studies demonstrate that GPR56 plays a role in brain development and tumorigenesis. Here, we report that human GPR56 undergoes GPS (GPCR proteolytic site)-mediated protein cleavage to generate its extracellular domain as an N-terminal fragment (GPR56-N). We also show that GPR56-N is highly glycosylated with N-linked carbohydrate chains. Mouse Gpr56 is ubiquitously expressed in various tissues, with high levels in kidney and pancreas. GPR56 mRNA is detected in diverse human cancer cells including pancreatic cancer cells PANC-1, Capan-1, and MiaCaPa-2. Interestingly, GPR56 protein is either negligible or undetectable in these pancreatic cancer cells, despite the fact that high levels of GPR56 mRNA are observed. Moreover, we have found that protein levels of GPR56 in pancreatic cancer cells were not affected when cells were treated with a proteasome inhibitor MG132. Taken together, these results define the biochemical properties of GPR56 protein, and suggest that the expression of GPR56 protein is suppressed in human pancreatic cancer cells.