The erythropoietin receptor transmembrane region is necessary for activation by the Friend spleen focus-forming virus gp55 glycoprotein.
The erythropoietin receptor (EPO-R), a member of the cytokine receptor superfamily, can be activated by binding either erythropoietin (EPO) or gp55, the Friend spleen focus-forming virus glycoprotein. The highly specific interaction between gp55 and EPO-R triggers cell proliferation and thereby causes the first stage of Friend virus-induced erythroleukemia. We have generated functional chimeric receptors containing regions of the EPO-R and the interleukin-3 receptor (AIC2A polypeptide), a related cytokine receptor which does not interact with gp55. All chimeric receptors were expressed at similar levels, had similar binding affinities for EPO, and conferred EPO-dependent cell growth. Only those chimeric receptors which contained the EPO-R transmembrane region were activated by gp55. These results demonstrate that the transmembrane region of the EPO-R is critical for activation by gp55. In addition, analysis of a soluble, secreted EPO-R and cysteine point mutants of the EPO-R show that the extracytoplasmic region of the EPO-R specifically interacts with gp55.
Zon
L I
LI
Department of Pediatrics, Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Moreau
J F
JF
Koo
J W
JW
Mathey-Prevot
B
B
D'Andrea
A D
AD
D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D007942:Leukemia, Experimental / Q000378:metabolism*; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017467:Receptors, Erythropoietin; D016185:Receptors, Interleukin-3 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013155:Spleen Focus-Forming Viruses / Q000378:metabolism*; D014162:Transfection; D014759:Viral Envelope Proteins / Q000378:metabolism*
D011956:Receptors, Cell Surface; D017467:Receptors, Erythropoietin; D016185:Receptors, Interleukin-3; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins