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PMID: 1320192 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The erythropoietin receptor transmembrane region is necessary for activation by the Friend spleen focus-forming virus gp55 glycoprotein.

Molecular and cellular biology ·Vol. 12 ·No. 7 ·1992-07-00 ·Pages 2949-57

Zon LI, Moreau JF, Koo JW, Mathey-Prevot B, D'Andrea AD

Abstract

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.

MeSH Terms
Binding Sites/genetics Cells, Cultured DNA Mutational Analysis Leukemia, Experimental/metabolism Protein Conformation Receptors, Cell Surface/genetics,metabolism Receptors, Erythropoietin Receptors, Interleukin-3/metabolism Recombinant Fusion Proteins/genetics,metabolism Signal Transduction Spleen Focus-Forming Viruses/metabolism Transfection Viral Envelope Proteins/metabolism
Chemicals
Receptors, Cell Surface Receptors, Erythropoietin Receptors, Interleukin-3 Recombinant Fusion Proteins Viral Envelope Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zon L I
Department of Pediatrics, Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Moreau J F
Koo J W
Mathey-Prevot B
D'Andrea A D
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.12.7.2949-2957.1992
Published
1992-07-00
Pages
2949-57
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC364508
Subset
IM
Grants
NHLBI NIH HHS · HL02347 · United States
NHLBI NIH HHS · P01 HL32262-10 · United States
External Links
PubMed source DOI: 10.1128/mcb.12.7.2949-2957.1992 PMC Full Text View journal details
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