Amino acid residues 268-276 of the erythropoietin receptor contain an endocytosis motif and are required for erythropoietin-mediated proliferation

Galit Flint-Ashtamker, Ronit Eisen-Lev, Jacob Cohen, Lily Jun-shen Huang, Drorit Neumann

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Erythropoietin (EPO) promotes viability, proliferation and differentiation of mammalian erythroid progenitor cells via its specific cell surface receptor (EPO-R). We have previously shown that truncated EPO-Rs containing 267 amino acids or less were defective in internalization of 125I-EPO, whereas internalization via a receptor derivative containing 276 amino acids was unaffected, thus directing focus to the nine amino acid residues FEGLFTTHK at positions 268-276 [Levin, Cohen, Supino, Yoshimura, Watowich, Neumann, FEBS Lett. 427 (1998) 164-170]. Here, a panel of EPO-R mutants was generated to determine the role of these residues in EPO endocytosis, down regulation of cell surface receptors and EPO-mediated signaling. While linking amino acid residues 268-276 to a truncated EPO-R (Δ+9 EPO-R) conferred both ligand uptake and ligand-independent down regulation of the respective receptor from the cell surface, Phe 272 was crucial for EPO endocytosis but not for ligand-independent down regulation. Additional receptor motifs probably play a role in EPO endocytosis and receptor down-regulation, as these processes were not adversely impaired in Δ268-276 EPO-R. A central role of residues 268-276, in particular Phe, was demonstrated by the inability of Δ268-276 and F268,272A EPO-Rs to support EPO-mediated signal transduction.

Original languageEnglish (US)
Pages (from-to)189-194
Number of pages6
JournalFEBS Letters
Volume518
Issue number1-3
DOIs
StatePublished - May 8 2002

Keywords

  • Endocytosis
  • Erythropoietin
  • Erythropoietin receptor
  • Tyr-phosphorylation

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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