Hematopoietic cell survival signals are elicited through non–tyrosine-containing sequences in the membrane-proximal region of the erythropoietin receptor (EPOR) by a Stat5-dependent pathway
- 作者：Yoon ; Donghoon ; Watowich ; Stephanie S.
- 刊名：Experimental Hematology
- 出版年：2003
- 期刊代码：100_0301472x
- 类别：med
- 出版时间：December, 2003
- 卷：31
- 期：12
- 页码：1310-1316
- 文件大小：181 K
摘要
Erythropoietin is essential for red blood cell development in vivo and is also an important therapeutic agent to treat anemia resulting from kidney failure or bone marrow suppression. The erythropoietin receptor (EPOR) elicits both positive and negative regulatory signaling pathways, primarily through phosphorylated tyrosine residues in the cytoplasmic domain of the activated receptor complex. Surprisingly, however, EPOR tyrosine residues are dispensable for in vivo erythropoiesis under nonstress conditions. One of the key signaling molecules elicited by the EPOR is the Stat5 transcription factor. Stat5 activation has been mapped to tyrosines 343 and 401 in the EPOR cytoplasmic region, although non-tyrosine-containing sequences in the EPOR cytoplasmic region can also stimulate Stat5. To test the functional role of non-tyrosine-containing sequences in the EPOR, we analyzed a series of mutant EPOR isoforms in cell survival and proliferation assays.