Homodimerization and constitutive activation of the erythropoietin receptor

Stephanie S. Watowich, Akihiko Yoshimura, Gregory D. Longmore, Douglas J. Hilton, Yuko Yoshimura, Harvey F. Lodish

Research output: Contribution to journalArticle

250 Citations (Scopus)

Abstract

The erythropoietin receptor (EPO-R) is a member of the recently described cytokine receptor superfamily. A constitutively active (hormone independent) form of the EPO-R was isolated that has a single amino acid change in the exoplasmic domain, converting arginine-129 to cysteine (R129C). Since EPO-Rs containing R129S, R129E, and R129P mutations are functionally wild type, the presence of cysteine at residue 129, and not the loss of arginine, is required for constitutive activity. Several mutant forms of the EPO-R were analyzed; all constitutively active mutants form disulfide-linked homodimers, whereas EPO-responsive or inactive forms of the receptor do not. Monomers and disulfide-linked dimers of the constitutive receptor are present on the plasma membrane and bind EPO with a single affinity. Homodimerization of the EPO-R is likely to play a role in ligand-induced signal transduction, and disulfide-linked dimerization of the constitutive receptor may mimic this step.

Original languageEnglish
Pages (from-to)2140-2144
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number6
Publication statusPublished - 1992
Externally publishedYes

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Erythropoietin Receptors
Disulfides
Cysteine
Arginine
Cytokine Receptors
Dimerization
Signal Transduction
Cell Membrane
Hormones
Ligands
Amino Acids
Mutation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Homodimerization and constitutive activation of the erythropoietin receptor. / Watowich, Stephanie S.; Yoshimura, Akihiko; Longmore, Gregory D.; Hilton, Douglas J.; Yoshimura, Yuko; Lodish, Harvey F.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 6, 1992, p. 2140-2144.

Research output: Contribution to journalArticle

Watowich, Stephanie S. ; Yoshimura, Akihiko ; Longmore, Gregory D. ; Hilton, Douglas J. ; Yoshimura, Yuko ; Lodish, Harvey F. / Homodimerization and constitutive activation of the erythropoietin receptor. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 6. pp. 2140-2144.
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