Glycosylation of KSHV Encoded vGPCR Functions in Its Signaling and Tumorigenicity
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 g...
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MDPI AG
2015-03-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/7/4/1627 |
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| author | Hui Wu Liqun Liu Jun Xiao Mengdie Chi Yixiao Qu Hao Feng |
| author_facet | Hui Wu Liqun Liu Jun Xiao Mengdie Chi Yixiao Qu Hao Feng |
| author_sort | Hui Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T04:28:02Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-19T04:28:02Z |
| publishDate | 2015-03-01 |
| publisher | MDPI AG |
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| series | Viruses |
| spelling | doaj.art-4252097a595549a9b5ee20ef13fd12332022-12-21T20:35:59ZengMDPI AGViruses1999-49152015-03-01741627164110.3390/v7041627v7041627Glycosylation of KSHV Encoded vGPCR Functions in Its Signaling and TumorigenicityHui Wu0Liqun Liu1Jun Xiao2Mengdie Chi3Yixiao Qu4Hao Feng5Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education of China, College of Life Science, Hunan Normal University, Changsha 410081, ChinaDivision of Pediatric Neurology, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha 410011, ChinaKey Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education of China, College of Life Science, Hunan Normal University, Changsha 410081, ChinaKey Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education of China, College of Life Science, Hunan Normal University, Changsha 410081, ChinaKey Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education of China, College of Life Science, Hunan Normal University, Changsha 410081, ChinaKey Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education of China, College of Life Science, Hunan Normal University, Changsha 410081, ChinaKaposi’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.http://www.mdpi.com/1999-4915/7/4/1627KSHVvGPCRGlycosylation |
| spellingShingle | Hui Wu Liqun Liu Jun Xiao Mengdie Chi Yixiao Qu Hao Feng Glycosylation of KSHV Encoded vGPCR Functions in Its Signaling and Tumorigenicity Viruses KSHV vGPCR Glycosylation |
| title | Glycosylation of KSHV Encoded vGPCR Functions in Its Signaling and Tumorigenicity |
| title_full | Glycosylation of KSHV Encoded vGPCR Functions in Its Signaling and Tumorigenicity |
| title_fullStr | Glycosylation of KSHV Encoded vGPCR Functions in Its Signaling and Tumorigenicity |
| title_full_unstemmed | Glycosylation of KSHV Encoded vGPCR Functions in Its Signaling and Tumorigenicity |
| title_short | Glycosylation of KSHV Encoded vGPCR Functions in Its Signaling and Tumorigenicity |
| title_sort | glycosylation of kshv encoded vgpcr functions in its signaling and tumorigenicity |
| topic | KSHV vGPCR Glycosylation |
| url | http://www.mdpi.com/1999-4915/7/4/1627 |
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