title: Glycosylation of KSHV encoded vGPCR functions in its signaling and tumorigenicity.
abstract: 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.
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education of China, College of Life Science, Hunan Normal University, Changsha 410081, China. wu2hui218@sina.com.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Division of Pediatric Neurology, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha 410011, China. llq91217@163.com.
authors.forename: Liqun
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education of China, College of Life Science, Hunan Normal University, Changsha 410081, China. zzz54120@hotmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education of China, College of Life Science, Hunan Normal University, Changsha 410081, China. chimengdie@163.com.
authors.forename: Mengdie
authors.initials: M
authors.lastname: Chi
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education of China, College of Life Science, Hunan Normal University, Changsha 410081, China. 15873156916@163.com.
authors.forename: Yixiao
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education of China, College of Life Science, Hunan Normal University, Changsha 410081, China. fenghao@hunnu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006031:Glycosylation; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000502:physiology*; D064593:Heterografts / Q000473:pathology; D051379:Mice; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009857:Oncogenes; D021381:Protein Transport; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D012514:Sarcoma, Kaposi / Q000473:pathology / Q000821:virology; D015398:Signal Transduction
chemical_list: C115448:G protein-coupled receptor, Human herpesvirus 8; D050505:Mutant Proteins; D019707:Receptors, Chemokine
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