title: The unsulfated extracellular N-terminus of vGPCR reduces the tumorigenicity of hGRO-α in nude mice.
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 [(35)S]-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.
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.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: YongMing
authors.initials: Y
authors.lastname: Fu
authors.forename: Jun
authors.initials: J
authors.lastname: Xiao
authors.forename: Man
authors.initials: M
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D041681:NIH 3T3 Cells; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014162:Transfection; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D054360:Chemokine CXCL1; D043562:Receptors, G-Protein-Coupled; D013431:Sulfates; D013462:Sulfur Radioisotopes; D014764:Viral Proteins; D014443:Tyrosine