Point mutation in the exoplasmic domain of the erythropoietin receptor resulting in hormone-independent activation and tumorigenicity

Akihiko Yoshimura, Gregory Longmore, Harvey F. Lodish

Research output: Contribution to journalArticle

229 Citations (Scopus)

Abstract

THE receptors for erythropoietin and other cytokines constitute a new superfamily1-4. They have no tyrosine-kinase or other enzyme motif and their signal-transducing mechanism is unclear. Here we describe two classes of activating mutations in the erythropoietin receptor (EPOR). A single point mutation in the exoplasmic domain enables it to induce hormone-independent cell growth and tumorigenesis after expression in nontumorigenic, interleukin-3-dependent haematopoietic cells. A C-terminal truncation in the cytoplasmic domain of the EPOR renders the receptor hyperresponsive to erythropoietin, but is insufficient to induce hormone-independent growth or tumorigenicity. The activating point mutation retards intracellular transport and turnover of the receptor. These alterations in metabolism and tumorigenicity caused by the EPOR with activating point mutations are similar to those observed in erythropoietin-independent activation of the wild type EPOR by association with gp55, the Friend spleen focus-forming virus glycoprotein 5,6.

Original languageEnglish
Pages (from-to)647-649
Number of pages3
JournalNature
Volume348
Issue number6302
Publication statusPublished - 1990 Dec 13
Externally publishedYes

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Erythropoietin Receptors
Point Mutation
Hormones
Erythropoietin
Interleukin-3
Protein-Tyrosine Kinases
Growth Hormone
Carcinogenesis
Cytokines
Mutation
Enzymes
Growth

ASJC Scopus subject areas

  • General

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Point mutation in the exoplasmic domain of the erythropoietin receptor resulting in hormone-independent activation and tumorigenicity. / Yoshimura, Akihiko; Longmore, Gregory; Lodish, Harvey F.

In: Nature, Vol. 348, No. 6302, 13.12.1990, p. 647-649.

Research output: Contribution to journalArticle

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