Ubiquitination regulates the internalization, endolysosomal sorting, and signaling of the erythropoietin receptor

Gamze Betul Bulut, Rita Sulahian, Yue Ma, Nai Wen Chi, Lily Jun Shen Huang

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Ubiquitination is a common mechanism of down-regulation of mitogenic receptors. Here, we show that ubiquitination of the erythropoietin receptor (EpoR) at Lys256 is necessary and sufficient for efficient Epo-induced receptor internalization, whereas ubiquitination at Lys 428 promotes trafficking of activated receptors to the lysosomes for degradation. Interestingly, EpoR that cannot be ubiquitinated has reduced mitogenic activities and ability to stimulate the STAT5, Ras/ MAPK, and PI3K/AKT signaling pathways. We therefore propose that ubiquitination of the EpoR critically controls both receptor down-regulation and downstream signaling.

Original languageEnglish (US)
Pages (from-to)6449-6457
Number of pages9
JournalJournal of Biological Chemistry
Volume286
Issue number8
DOIs
StatePublished - Feb 25 2011

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Erythropoietin Receptors
Ubiquitination
Sorting
Down-Regulation
Phosphatidylinositol 3-Kinases
Lysosomes
Degradation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Ubiquitination regulates the internalization, endolysosomal sorting, and signaling of the erythropoietin receptor. / Bulut, Gamze Betul; Sulahian, Rita; Ma, Yue; Chi, Nai Wen; Huang, Lily Jun Shen.

In: Journal of Biological Chemistry, Vol. 286, No. 8, 25.02.2011, p. 6449-6457.

Research output: Contribution to journalArticle

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