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

FEBS Letters

Eisen-Lev, Ronit¹  Cohen, Jacob¹  Flint-Ashtamker, Galit¹  Jun-shen Huang, Lily²  Neumann, Drorit¹ 

[1] Department of Cell Biology and Histology, Sackler Faculty of Medicine Tel-Aviv University, Ramat Aviv 69978, Israel;Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA

关键词: Erythropoietin;    Erythropoietin receptor;    Endocytosis;    Tyr-phosphorylation;    EPO;    erythropoietin;    EPO-R;    erythropoietin receptor;    JAK2;    Janus kinase 2;   

DOI  :  10.1016/S0014-5793(02)02691-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown