Erythropoietin induces activation of Stat5 through association with specific tyrosines on the receptor that are not required for a mitogenic response.
Erythropoietin induces activation of Stat5 through association with specific tyrosines on the receptor that are not required for a mitogenic response.
复制标题
促红细胞生成素通过与有丝分裂反应不需要的受体上的特定酪氨酸结合来诱导 Stat5 的激活。
DOI：
10.1128/mcb.16.4.1622
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发表时间：
1996
影响因子：
5.3
通讯作者：
Ihle,JN
中科院分区：
文献类型：
--
作者：
Quelle,FW;Wang,D;Nosaka,T;Thierfelder,WE;Stravopodis,D;Weinstein,Y;Ihle,JN
The cytoplasmic domain of the erythropoietin receptor (EpoR) contains a membrane-distal region that is dispensable for mitogenesis but is required for the recruitment and tyrosine phosphorylation of a variety of signaling proteins. The membrane-proximal region of 96 amino acids is necessary and sufficient for mitogenesis as well as Jak2 activation, induction of c-fos, c-myc, cis, the T-cell receptor γ locus (TCR-γ), and c-pim-1.The studies presented here demonstrate that this region is also necessary and sufficient for the activation of Stat5A and Stat5B. The membrane-proximal domain contains a single tyrosine, Y-343, which when mutated eliminates the ability of the receptor to couple Epo binding to the activation of Stat5. Furthermore, peptide competitions demonstrate that this site, when phosphorylated, can disrupt Stat5 DNA binding activity, consistent with a role of Y-343 as a site of recruitment to the receptor. Cells expressing the truncated, Y343F mutant (a mutant with a Y-to-F alteration at position 343) proliferate in response to Epo in a manner comparable to that of the controls. However, in these cells, Epo stimulation does not induce the appearance of transcripts forcis, TCR-γ, or c-fos, suggesting a role for Stat5 in their regulation.
