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

ABSTRACT: Ubiquitination is a common mechanism of down-regulation of mitogenic receptors. Here, we show that ubiquitination of the erythropoietin receptor (EpoR) at Lys(256) 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.

SUBMITTER: Bulut GB

PROVIDER: S-EPMC3057794 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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

Bulut Gamze Betul GB Sulahian Rita R Ma Yue Y Chi Nai-wen NW Huang Lily Jun-shen LJ

The Journal of biological chemistry 20101223 8

Ubiquitination is a common mechanism of down-regulation of mitogenic receptors. Here, we show that ubiquitination of the erythropoietin receptor (EpoR) at Lys(256) 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 si ...[more]

PMID: 21183685

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