Wu Hui, Liu Liqun, Xiao Jun, Chi Mengdie, Qu Yixiao, Feng Hao
Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education of China, College of Life Science, Hunan Normal University, Changsha 410081, China.
Division of Pediatric Neurology, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
Viruses. 2015 Mar 31;7(4):1627-41. doi: 10.3390/v7041627.
Kaposi's sarcoma-associated herpesvirus (KSHV) is a tumor virus and the etiologic agent of Kaposi's Sarcoma (KS). KSHV G protein-coupled receptor (vGPCR) is an oncogene that is implicated in malignancies associated with KHSV infection. In this study, we show that vGPCR undergoes extensive N-linked glycosylation within the extracellular domains, specifically asparagines 18, 22, 31 and 202. An immunofluorescence assay demonstrates that N-linked glycosylation are necessary for vGPCR trafficking to the cellular membrane. Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. These findings support the conclusion that glycosylation is critical for vGPCR tumorigenesis and imply that chemokine regulation at the plasma membrane is crucial for vGPCR mediated signaling.
卡波西肉瘤相关疱疹病毒（KSHV）是一种肿瘤病毒，也是卡波西肉瘤（KS）的病原体。KSHV G蛋白偶联受体（vGPCR）是一种癌基因，与KHSV感染相关的恶性肿瘤有关。在本研究中，我们发现vGPCR在细胞外结构域内经历广泛的N-糖基化，特别是天冬酰胺18、22、31和202。免疫荧光测定表明，N-糖基化对于vGPCR转运到细胞膜是必需的。利用糖基化位点被切除的vGPCR突变体，我们发现这些vGPCR突变体在培养细胞中未能激活下游信号，并且在异种移植裸鼠模型中诱导肿瘤形成的能力严重受损。这些发现支持了糖基化对于vGPCR肿瘤发生至关重要的结论，并暗示质膜上的趋化因子调节对于vGPCR介导的信号传导至关重要。
