TY - JOUR
T1 - Ubiquitination regulates the internalization, endolysosomal sorting, and signaling of the erythropoietin receptor
AU - Bulut, Gamze Betul
AU - Sulahian, Rita
AU - Ma, Yue
AU - Chi, Nai Wen
AU - Huang, Lily Jun Shen
PY - 2011/2/25
Y1 - 2011/2/25
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M110.186890
DO - 10.1074/jbc.M110.186890
M3 - Article
C2 - 21183685
AN - SCOPUS:79953188365
SN - 0021-9258
VL - 286
SP - 6449
EP - 6457
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 8
ER -