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

Journal Article · Fri Sep 01 00:00:00 EDT 1989 · Journal of Virology; (USA)

OSTI ID:7152047

Gliniak, B C; Kabat, D ^[1]

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1. Oregon Health Sciences Univ., Portland (USA)

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. The authors 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. They 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.

• OSTI ID: 7152047
• Journal Information: Journal of Virology; (USA), Vol. 63:9; ISSN 0022-538X
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GLYCOPROTEINS
MEMBRANE TRANSPORT
TUMOR CELLS
AUTORADIOGRAPHY
VIRUSES
MOLECULAR BIOLOGY
CELL MEMBRANES
CHEMICAL BONDS
ELECTROPHORESIS
IODINE 125
MICE
MOLECULAR STRUCTURE
SUBCELLULAR DISTRIBUTION
SULFUR 35
TRACER TECHNIQUES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CELL CONSTITUENTS
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MEMBRANES
MICROORGANISMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PARASITES
PROTEINS
RADIOISOTOPES
RODENTS
SULFUR ISOTOPES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques