Friend spleen focus-forming virus glycoprotein gp55 interacts with the erythropoietin receptor in the endoplasmic reticulum and affects receptor metabolism.
The Friend spleen focus-forming virus envelope glycoprotein, gp55, binds to the murine erythropoietin receptor (EPO-R) and triggers growth activation in the absence of EPO. Interleukin 3-dependent lymphoid cell lines that have been stably transfected with the EPO-R cDNA grow in the presence of EPO or interleukin 3. In these cells, the EPO-R is synthesized as a minor 62-kDa unglycosylated form and a major 64-kDa form carrying one high-mannose N-linked oligosaccharide. A fraction of the 64-kDa form is processed to a 66-kDa species with complex-type sugars. Very little of the EPO-R is expressed on the cell surface and all three forms of EPO-R are degraded rapidly. Cells transfected with both EPO-R and gp55 cDNAs grow in the absence of EPO. Most of the EPO-R associated with gp55 is endoglycosidase H-sensitive, suggesting that the interactions between these proteins occur in the endoplasmic reticulum. Furthermore, the endoglycosidase H-sensitive EPO-R is more stable than in the absence of gp55, a result suggesting that interaction of gp55 with the EPO-R causes it to remain within the rough endoplasmic reticulum. It is possible that gp55 EPO-R complexes within this compartment send a growth-promoting signal to the cell.
Yoshimura
A
A
Whitehead Institute for Biomedical Research, Nine Cambridge Center, MA 02142.
D'Andrea
A D
AD
Lodish
H F
HF
D000818:Animals; D002451:Cell Compartmentation; D002455:Cell Division; D019286:Endopeptidase K; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism; D015686:Gene Products, env / Q000378:metabolism*; D006596:Hexosaminidases / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D012697:Serine Endopeptidases / Q000494:pharmacology
D015686:Gene Products, env; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D006596:Hexosaminidases; D012697:Serine Endopeptidases; D019286:Endopeptidase K