title: Leukemogenic membrane glycoprotein encoded by Friend spleen focus-forming virus: transport to cell surfaces and shedding are controlled by disulfide-bonded dimerization and by cleavage of a hydrophobic membrane anchor.
abstract: The leukemogenic glycoprotein (gp55) encoded by Friend spleen focus-forming virus is predominantly retained in the rough endoplasmic reticulum (RER). However, a small proportion (ca. 5%) is processed to form a derivative that occurs on plasma membranes and causes mitosis of infected erythroblasts. We have now found that gp55 folds heterogeneously in the RER to form components with different disulfide bonds and that this difference may determine their processing fates. RER gp55 consists predominantly of monomers with intrachain disulfide bonds. In contrast, the processed molecules are disulfide-bonded dimers. These dimers are extensively modified in transit to cell surfaces by conversion of four N-linked high-mannose oligosaccharides to complex derivatives and by attachment of a sialylated O-linked oligosaccharide. The plasma membrane dimers are then slowly shed into the medium by a mechanism that involves proteolytic cleavage of approximately 25 membrane-anchoring hydrophobic amino acids from the carboxyl termini of the glycoproteins. Consequently, shed molecules have shorter polypeptide chains than cell-associated gp55. We conclude that gp55 folds into different disulfide-bonded components that do not substantially isomerize, and that only one specific dimer is competent for export from the RER. Mitogenic activity of gp55 could be caused by the cell surface dimers, by the shed derivative, or by the carboxyl-terminal hydrophobic anchors that remain in the membranes after the shedding reaction.
authors.affiliation: Department of Biochemistry, School of Medicine, Oregon Health Sciences University, Portland 97201-3098.
authors.forename: B C
authors.initials: BC
authors.lastname: Gliniak
authors.forename: D
authors.initials: D
authors.lastname: Kabat
mesh_terms: D001692:Biological Transport; D004220:Disulfides; D004721:Endoplasmic Reticulum / Q000378:metabolism; D009052:Leukemia Virus, Murine / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008970:Molecular Weight; D013155:Spleen Focus-Forming Viruses / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000032:analysis / Q000378:metabolism*
chemical_list: D004220:Disulfides; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins