Impaired activation and binding of the erythropoietin receptor by a mutant gp55 of Friend spleen focus-forming virus, which has a cytoplasmic domain.
A murine erythroleukemogenic retrovirus, Friend spleen focus-forming virus, encodes an envelope protein-like membrane glycoprotein (gp55) in its defective env gene which is responsible for activation of the erythropoietin receptor (EpoR) and the abnormally rapid proliferation of erythroid precursor cells. The S34 mutant gp55, which possesses an additional cytoplasmic domain, is nonpathogenic and its processing to the cell surface is severely reduced compared to that of the wild-type gp55. In this study, we found that the S34 mutant gp55 neither binds to nor activates the EpoR. The S34 mutant gp55 formed disulfide-bonded homodimers in the rough endoplasmic reticulum (RER) membrane much less efficiently than the wild-type gp55, which is consistent with the proposal that homodimer formation is a prerequisite for gp55 to be exported from the RER. We found that the wild-type gp55 that is bound to EpoR in the RER consists of a large number of monomers and a small number of dimers, suggesting that monomers of the S34 mutant gp55 have lost the ability to bind to the EpoR. The 1-bp insertion present in the wild-type gp55 gene, causing a loss of the cytoplasmic domain, is essential for pathogenicity in that it renders the encoded protein capable of both binding to the EpoR and transport to the cell surface.
Yugawa
T
T
Laboratory of Molecular Cell Science, Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Amanuma
H
H
D000818:Animals; D002460:Cell Line; D019281:Dimerization; D004220:Disulfides; D004921:Erythropoietin / Q000494:pharmacology; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D009154:Mutation; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism*; D013155:Spleen Focus-Forming Viruses / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
D004220:Disulfides; D008562:Membrane Glycoproteins; D008934:Mitogens; D017467:Receptors, Erythropoietin; D014759:Viral Envelope Proteins; C078780:glycoprotein gp55, Friend spleen focus-forming virus; D004921:Erythropoietin