Ubiquitination Regulates the Internalization, Endolysosomal Sorting, and Signaling of the Erythropoietin Receptor

• Published in: The Journal of biological chemistry Vol. 286; no. 8; pp. 6449 - 6457
• Main Authors: Bulut, Gamze Betul, Sulahian, Rita, Ma, Yue, Chi, Nai-wen, Huang, Lily Jun-shen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.02.2011; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Cytokine; Down-Regulation - physiology; Endosomes - genetics; Endosomes - metabolism; Intracellular Trafficking; Mice; Mitogen-Activated Protein Kinase Kinases - genetics; Mitogen-Activated Protein Kinase Kinases - metabolism; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Protein Transport - physiology; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; ras Proteins - genetics; ras Proteins - metabolism; Receptor Endocytosis; Receptors, Erythropoietin - genetics; Receptors, Erythropoietin - metabolism; Signal Transduction; Signal Transduction - physiology; STAT5 Transcription Factor - genetics; STAT5 Transcription Factor - metabolism; Ubiquitination; Ubiquitination - physiology; Intracellular Trafficking; Ubiquitination; Receptor Endocytosis; Signal Transduction; Cytokine

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 Lys428 promotes trafficking of a...