title: GPS autoproteolysis is required for CD97 to up-regulate the expression of N-cadherin that promotes homotypic cell-cell aggregation.
abstract: Most adhesion-class G protein-coupled receptors (adhesion-GPCRs) undergo a novel self-catalytic cleavage at the GPCR proteolysis site (GPS) to form a hetero-dimeric complex containing the extracellular and seven-span transmembrane subunits. However, little is known about the role of GPS auto-proteolysis in the function of adhesion-GPCRs. Here we show that GPS cleavage is essential for the homotypic cell aggregation promoted by CD97 receptor, a leukocyte-restricted adhesion-GPCR often aberrantly expressed in carcinomas. We find that CD97 does not mediate cell aggregation directly. Instead, expression of the wild type - but not the GPS cleavage-deficient CD97 up-regulates the expression of N-cadherin, leading to Ca(++)-dependent cell-cell aggregation. Our results provide a clear evidence for the role of GPS proteolytic modification in the cellular function of adhesion-GPCRs.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.
authors.forename: Cheng-Chih
authors.initials: CC
authors.lastname: Hsiao
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Chen
authors.forename: Gin-Wen
authors.initials: GW
authors.lastname: Chang
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Lin
mesh_terms: D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D015820:Cadherins / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics*; D002449:Cell Aggregation / Q000235:genetics; D002460:Cell Line; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D015854:Up-Regulation
chemical_list: C095004:ADGRE5 protein, human; D015703:Antigens, CD; D015820:Cadherins; D043562:Receptors, G-Protein-Coupled; D010447:Peptide Hydrolases