Hsiao Cheng-Chih, Cheng Kai-Fong, Chen Hsin-Yi, Chou Yi-Hua, Stacey Martin, Chang Gin-Wen, Lin Hsi-Hsien
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-San, Tao-Yuan, Taiwan.
FEBS Lett. 2009 Oct 6;583(19):3285-90. doi: 10.1016/j.febslet.2009.09.001. Epub 2009 Sep 6.
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.
G蛋白偶联受体（GPCR）蛋白水解位点（GPS）处的自蛋白水解是黏附GPCR的一个标志。尽管GPS自蛋白水解缺陷与遗传疾病有关，但其调控信息仍然难以捉摸。在这里，我们研究了CD97的GPS蛋白水解，CD97是一种人类白细胞限制性和肿瘤相关的黏附GPCR。我们发现，与它的紧密同源物含表皮生长因子样模块的黏蛋白样激素受体2不同，CD97的加工不完全。在相关黏附GPCR的GPS基序内鉴定出一种独特的N-糖基化模式。使用N-糖基化抑制剂和突变体证实，位点特异性N-糖基化是CD97中GPS蛋白水解的一个重要决定因素。我们的结果表明，N-糖基化可能调节黏附GPCR的加工过程，从而导致产生裂解或未裂解的分子。
