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J Biol Chem. 1993 Mar 15;268(8):5741-7.

Cell surface site for mitogenic interaction of erythropoietin receptors with the membrane glycoprotein encoded by Friend erythroleukemia virus.

Author information

1
Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health Sciences University, Portland 97201-3098.

Abstract

The membrane glycoprotein (gp55) encoded by the env gene of Friend spleen focus-forming virus (SFFV) causes mitogenesis of infected erythroblasts and is inefficiently (3-5%) processed from the rough endoplasmic reticulum (RER) to plasma membranes. Recent evidence suggested that gp55 binds to erythropoietin receptors (EpoR) in the RER, and it was proposed that this intracellular interaction causes mitogenesis (Li, J.-P., D'Andrea, A. D., Lodish, H. F., and Baltimore, D. (1990) Nature 343, 762-764). Other evidence has indicated that the plasma membrane component (gp55P) can also complex with EpoR. To identify the site of functional complexes and to study the factors that control their formation, we analyzed eight SFFV env mutants that contain in-frame deletions or linker insertions. The three nonpathogenic mutants encode gp55s that fail to leave the RER, whereas the five pathogenic mutants encode glycoproteins that occur on cell surfaces. Although BaF3 hematopoietic cells are interleukin 3 (IL-3)-dependent, a cellular derivative BaF3/EpoR that contains EpoR survives and grows in either IL-3 or erythropoietin (Epo). The five pathogenic SFFV env mutants converted BaF3/EpoR but not BaF3 cells to growth factor independence, whereas the nonpathogenic mutants did not eliminate growth factor requirements of any cells. Studies using 125I-Epo and the covalent cross-linking reagent disuccinimidyl suberate provided unambiguous evidence for ternary complexes of 125I-Epo.EpoR.gp55P on surfaces of all factor-independent cells. Size of the cell surface complex was correspondingly reduced in the case of a newly isolated SFFV mutant that encodes a severely truncated (M(r) approximately 41,000) but mitogenically active env glycoprotein. Our results support the hypothesis that activation of EpoR by the SFFV env glycoprotein occurs exclusively on cell surfaces.

PMID:
8449938
[Indexed for MEDLINE]
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