Abstract
The Kaposi’s Sarcoma-associated Herpesvirus (KSHV)-encoded G-protein coupled receptor (vGPCR) is an oncoprotein that is implicated in KSHV-associated malignancies. We previously revealed vGPCR incorporates sulfate groups within its extracellular N-terminal tyrosine residues (Y26 and Y28) and that this tyrosine sulfation is crucial for its tumorigenicity in nude mice. hGRO-α binds vGPCR in a sulfotyrosine-dependent manner and promotes its tumorigenicity through autocrine signaling. Interestingly, an unsulfated vGPCR mutant (yydd-vGPCR) attenuated the tumor growth triggered by hGRO-α. In this study, the extracellular N-terminus of vGPCR (wt-vGN) and an unsulfated vGPCR mutant (yydd-vGN) were individually secreted, expressed and purified. A radioactive labeling assay demonstrated that wt-vGN but not yydd-vGN incorporated [35S]-sulfate. In nude mice, NIH3T3 cells expressing yydd-vGN but not wt-vGN could significantly inhibit the tumor growth triggered by hGRO-α. All our data support the conclusion that the unsulfated extracellular N-terminus of vGPCR reduces the tumorigenicity of hGRO-α.
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Wu, H., Fu, Y., Xiao, J. et al. The unsulfated extracellular N-terminus of vGPCR reduces the tumorigenicity of hGRO-α in nude mice. Sci. China Life Sci. 56, 26–31 (2013). https://doi.org/10.1007/s11427-012-4405-9
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DOI: https://doi.org/10.1007/s11427-012-4405-9