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首页> 外文期刊>Oncogene >GPR56 is a GPCR that is overexpressed in gliomas and functions in tumor cell adhesion
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GPR56 is a GPCR that is overexpressed in gliomas and functions in tumor cell adhesion

机译：GPR56是在神经胶质瘤中过表达并在肿瘤细胞粘附中起作用的GPCR

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GPR56 (also known as TM7XN1) is a newly discovered orphan G-protein-coupled receptor (GPCR) of the secretin family that has a role in the development of neural progenitor cells and has been linked to developmental malformations of the human brain. GPR56 diverges from other secretin-like family members in that it has an extremely large N-terminal extracellular region (381 amino acids) and contains a novel feature among this new subclass, consisting of four cysteine residues that define a GPCR proteolytic site (GPS motif) located just before the first transmembrane spanning domain. The rest of the amino-terminal domain contains a large number of possible N- and O-linked glycosylation sites similar to mucin-like proteins. These features suggest a role in cell–cell, or cell–matrix interactions. Here, we demonstrate upregulation of GPR56 in glioblastoma multiforme tumors using functional genomics. Immunohistochemistry studies confirmed the expression of GPR56 protein in a majority of glioblastoma/astrocytoma tumor samples with undetectable levels of expression in normal adult brain tissue. Immunofluorescence analysis of human glioma cells using anti-GPR56 antibodies demonstrate that GPR56 is expressed on the leading edge of membrane filopodia and colocalizes with -actinin. Purified recombinant GPR56 extracellular domain protein inhibits glioma cell adhesion and causes abnormal cytoskeletal morphology and cell rounding. These results indicate that the extracellular domain may compete for unidentified ligand(s), and block the normal function of GPR56 in cell attachment. In reporter assays, overexpression of GPR56 activates the NF-B, PAI-1 and TCF transcriptional response elements. These pathways have been implicated in cytoskeletal signaling, adhesion and tumor biology. The above results indicate that GPR56 serves as an adhesion GPCR and is involved in adhesion signaling.
机译：GPR56（也称为TM7XN1）是促胰液素家族新发现的孤儿G蛋白偶联受体（GPCR），在神经祖细胞的发育中起作用，并与人脑的发育畸形有关。 GPR56与其他促胰液素样家族成员不同，因为它具有一个非常大的N末端胞外区（381个氨基酸），并且在这个新的亚类中包含一个新功能，该亚类由四个半胱氨酸残基组成，这些残基定义了GPCR的蛋白水解位点（GPS基序）位于第一个跨膜跨越域之前。其余的氨基末端结构域包含大量类似于粘蛋白样蛋白的可能的N和O联糖基化位点。这些特征表明在细胞之间或细胞与基质的相互作用中起作用。在这里，我们展示了使用功能基因组学在多形性胶质母细胞瘤中GPR56的上调。免疫组织化学研究证实，大多数成胶质细胞瘤/星形胶质细胞瘤样品中GPR56蛋白的表达在正常成人脑组织中均未检测到表达水平。使用抗GPR56抗体对人神经胶质瘤细胞进行的免疫荧光分析表明，GPR56在膜丝状伪足的前缘表达，并与-actinin共定位。纯化的重组GPR56细胞外域蛋白抑制神经胶质瘤细胞粘附，并导致异常的细胞骨架形态和细胞变圆。这些结果表明，细胞外结构域可能竞争未鉴定的配体，并阻断GPR56在细胞附着中的正常功能。在报告基因检测中，GPR56的过度表达激活了NF-B，PAI-1和TCF转录反应元件。这些途径与细胞骨架信号传导，粘附和肿瘤生物学有关。以上结果表明，GPR56用作粘附GPCR，并参与粘附信号传导。

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