A cytosolic domain of the erythropoietin receptor contributes to endoplasmic reticulum-associated degradation

Lia Supino-Rosin, Akihiko Yoshimura, Hanna Altaratz, Drorit Neumann

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The erythropoietin receptor (EPO-R) is the cellular target for erythropoietin (EPO), the primary hormone that mediates the proliferation of immature erythroblasts and their differentiation into mature erythrocytes. Unusual features of the EPO-R are its short half-life (t( 1/2 ) 1-2 h), its degradation via multiple pathways and the fact that less than 1% of total cellular EPO-R molecules are found on the cell surface. The contribution of EPO-R structural determinants to the regulation of its intracellular metabolism is still unclear. The epidermal growth factor receptor (EGF-R), unlike the EPO-R, is efficiently transported to the cell surface and displays a much longer metabolic half-life. To determine which EPO-R cytosolic domains are involved in intracellular degradation, we studied chimeric receptor molecules constructed of EGF-R extracellular and transmembrane parts, linked to the full length or truncated cytosolic part of the EPO-R. The chimeras were expressed in transiently transfected COS 7 cells and stably expressed in Ba/F3 cells. Our experiments indicate that the cytosolic part of the EPO-R contains determinants that mark it for rapid degradation, in association with the endoplasmic reticulum (ER). This degradation was insensitive to brefeldin A and was inhibited by specific proteasomal inhibitors. A truncated EGF- R/EPO-R chimera containing only 50 amino acids of the EPO-R membrane-proximal cytosolic part was also rapidly degraded suggesting that these 50 amino acids are involved in receptor degradation.

Original languageEnglish
Pages (from-to)410-419
Number of pages10
JournalEuropean Journal of Biochemistry
Volume263
Issue number2
DOIs
Publication statusPublished - 1999 Jul 15
Externally publishedYes

    Fingerprint

Keywords

  • Chimeras
  • Degradation
  • Endoplasmic reticulum
  • Epidermal growth factor receptor
  • Erythropoietin receptor

ASJC Scopus subject areas

  • Biochemistry

Cite this