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Site-specific N-glycosylation regulates the GPS auto-proteolysis of CD97 |
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| Authors: | Cheng-Chih Hsiao Kai-Fong Cheng Yi-Hua Chou Gin-Wen Chang |
| Institution: | a Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-San, Tao-Yuan, Taiwan b Department of Microbiology and Immunology, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-San, Tao-Yuan, Taiwan c Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK |
| 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. |
| Keywords: | 7TM seven-transmembrane DOC degree of cleavage ECD extracellular domain EGF-TM7 epidermal growth factor module-containing seven-transmembrane receptor EMR2 epidermal growth factor-like module-containing mucin-like hormone receptor 2 Fc fragment crystallisable GPCR G protein-coupled receptor GPS GPCR proteolytic site PARs protease-activated receptors WT wild-type |
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