Department of Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
J Biol Chem. 2011 Feb 25;286(8):6449-57. doi: 10.1074/jbc.M110.186890. Epub 2010 Dec 23.
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.
泛素化是下调有丝分裂原受体的常见机制。在这里，我们表明，Epo 受体（EpoR）赖氨酸（256）上的泛素化对于有效的 Epo 诱导的受体内化是必需和充分的，而赖氨酸（428）上的泛素化促进激活的受体向溶酶体运输以进行降解。有趣的是，不能泛素化的 EpoR 具有降低的有丝分裂活性和刺激 STAT5、Ras/MAPK 和 PI3K/AKT 信号通路的能力。因此，我们提出 EpoR 的泛素化对于受体下调和下游信号传导都具有关键性的控制作用。
