title: Site-specific N-glycosylation regulates the GPS auto-proteolysis of CD97.
abstract: Auto-proteolysis at the G protein-coupled receptor (GPCR) proteolytic site (GPS) is a hallmark of adhesion-GPCRs. Although defects in GPS auto-proteolysis have been linked to genetic disorders, information on its regulation remains elusive. Here, we investigated the GPS proteolysis of CD97, a human leukocyte-restricted and tumor-associated adhesion-GPCR. We found that CD97 is incompletely processed, unlike its close homolog, epidermal growth factor-like module-containing mucin-like hormone receptor 2. A unique pattern of N-glycosylation within the GPS motif of related adhesion-GPCRs was identified. The use of N-glycosylation inhibitors and mutants confirm site-specific N-glycosylation is an important determinant of GPS proteolysis in CD97. Our results suggest that N-glycosylation may regulate the processing of adhesion-GPCRs leading to the production of either cleaved or uncleaved molecules.
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-San, Tao-Yuan, Taiwan.
authors.forename: Cheng-Chih
authors.initials: CC
authors.lastname: Hsiao
authors.forename: Kai-Fong
authors.initials: KF
authors.lastname: Cheng
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Chen
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Chou
authors.forename: Martin
authors.initials: M
authors.lastname: Stacey
authors.forename: Gin-Wen
authors.initials: GW
authors.lastname: Chang
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Lin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D006031:Glycosylation; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: C095004:ADGRE5 protein, human; D015703:Antigens, CD; D008562:Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled