Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Inactivation of erythropoietin receptor function by point mutations in a region having homology with other cytokine receptors

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Miura, O.
  • Cleveland, John
  • Ihle, J. N.

publication date

  • March 1993

journal

  • Molecular and Cellular Biology  Journal

abstract

  • The cytoplasmic domain of the erythropoietin receptor (EpoR) contains a region, proximal to the transmembrane domain, that is essential for function and has homology with other members of the cytokine receptor family. To explore the functional significance of this region and to identify critical residues, we introduced several amino acid substitutions and examined their effects on erythropoietin-induced mitogenesis, tyrosine phosphorylation, and expression of immediate-early (c-fos, c-myc, and egr-1) and early (ornithine decarboxylase and T-cell receptor gamma) genes in interleukin-3-dependent cell lines. Amino acid substitution of W-282, which is strictly conserved at the middle portion of the homology region, completely abolished all the functions of the EpoR. Point mutation at L-306 or E-307, both of which are in a conserved LEVL motif, drastically impaired the function of the receptor in all assays. Other point mutations, introduced into less conserved amino acid residues, did not significantly impair the function of the receptor. These results demonstrate that conserved amino acid residues in this domain of the EpoR are required for mitogenesis, stimulation of tyrosine phosphorylation, and induction of immediate-early and early genes.

subject areas

  • Amino Acid Sequence
  • Animals
  • Cell Division
  • Cell Line, Transformed
  • Cytokines
  • Enzyme Induction
  • Erythropoietin
  • Interleukin-3
  • Leukemia, Myeloid
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Point Mutation
  • Protein-Tyrosine Kinases
  • Receptors, Cell Surface
  • Receptors, Erythropoietin
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship
  • Transcription, Genetic
scroll to property group menus

Identity

PubMed Central ID

  • PMC359491

International Standard Serial Number (ISSN)

  • 0270-7306

PubMed ID

  • 8382775
scroll to property group menus

Additional Document Info

start page

  • 1788

end page

  • 1795

volume

  • 13

issue

  • 3

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support