Identification of tyrosine residues within the intracellular domain of the erythropoietin receptor crucial for STAT5 activation
Identification of tyrosine residues within the intracellular domain of the erythropoietin receptor crucial for STAT5 activation
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DOI：
10.1002/j.1460-2075.1996.tb00601.x
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发表时间：
1996-05-15
期刊：
影响因子：
11.4
通讯作者：
Mayeux, P
中科院分区：
文献类型：
--
作者：
Gobert, S;Chretien, S;Mayeux, P
FDCP-1细胞是造血祖细胞，其需要白细胞介素-3以存活和增殖，用鼠促红细胞生成素受体cDNA稳定转染的FDCP-1细胞在促红细胞生成素存在下存活和增殖。促红细胞生成素诱导细胞中STAT 5的短形式（80 kDa）的活化。在表达促红细胞生成素受体突变变体的细胞中，促红细胞生成素诱导的STAT 5活化强烈降低，其中其细胞内结构域中的酪氨酸残基已被消除。我们确定促红细胞生成素受体酪氨酸残基343和401是STAT 5激活所必需的。这两个酪氨酸残基周围的氨基酸序列非常相似。包含磷酸化Tyr 343或磷酸化Tyr 401的肽，但不包含其未磷酸化的对应物，抑制STAT 5活化。我们建议，这两个酪氨酸残基的促红细胞生成素受体构成的STAT 5 SH 2结构域的对接站点，促红细胞生成素介导的生长刺激减少在细胞表达促红细胞生成素受体缺乏Tpr 343和Tyr 401。这表明STAT 5激活可能参与FDCP-1细胞的生长控制。
FDCP-1 cells are hematopoietic progenitor cells which require interleukin-3 for survival and proliferation, FDCP-1 cells stably transfected with the murine erythropoietin receptor cDNA survive and proliferate in the presence of erythropoietin. Erythropoietin induces the activation of the short forms (80 kDa) of STAT5 in the cells. Erythropoietin-induced activation of STAT5 was strongly reduced in cells expressing mutated variants of the erythropoietin receptors in which tyrosine residues in their intracellular domain have been eliminated. We determined that the erythropoietin receptor tyrosine residues 343 and 401 are independently necessary for STAT5 activation. The amino acid sequences surrounding these two tyrosine residues are very similar, Peptides comprising either phosphorylated Tyr343 or phosphorylated Tyr401, but not their unphosphorylated counterparts, inhibited the STAT5 activation. We propose that these two tyrosine residues of the erythropoietin receptor constitute docking sites for the STAT5 SH2 domain, The growth stimulus mediated by erythropoietin was decreased in cells expressing erythropoietin receptors lacking both Tpr343 and Tyr401. This suggests that STAT5 activation could be involved in the growth control of FDCP-1 cells.