Yoshimura A, Misawa H
Institute of Life Science, Kurume University, Japan.
Curr Opin Hematol. 1998 May;5(3):171-6. doi: 10.1097/00062752-199805000-00004.
Interaction between erythropoietin (EPO) and its membrane receptor induces the proliferation and differentiation of erythroid progenitors. Targeted disruption of the EPO receptor (EPOR) gene have clearly demonstrated the importance of the EPO/EPOR system for definitive erythroid cell survival and proliferation; however, in vitro rescue experiments have revealed that it is not essential for differentiation. The three-dimensional structure of the EPOR has been determined, and a biologically active 20 amino acid peptide has been shown to cause dimerization of the extracellular domain of EPOR. EPO activates the JAK2-STAT5 pathway, and two tyrosine residues (Y343, Y401) in the cytoplasmic domain of EPOR are important for STAT5 activation. However, the physiologic role of STAT5 in erythroid cell proliferation and differentiation is still controversial. Mutations that result in C-terminal deletion of EPOR are frequently found in familial erythrocytosis. Hematopoietic cell phosphatase, which binds to the C-terminal region, could be involved in negative regulation of EPOR function.
促红细胞生成素（EPO）与其膜受体之间的相互作用可诱导红系祖细胞的增殖和分化。对促红细胞生成素受体（EPOR）基因进行靶向破坏已清楚地证明了EPO/EPOR系统对于确定的红系细胞存活和增殖的重要性；然而，体外挽救实验表明它对于分化并非必不可少。EPOR的三维结构已被确定，并且一种具有生物活性的20个氨基酸的肽已被证明可导致EPOR细胞外结构域的二聚化。EPO激活JAK2-STAT5途径，并且EPOR细胞质结构域中的两个酪氨酸残基（Y343、Y401）对于STAT5激活很重要。然而，STAT5在红系细胞增殖和分化中的生理作用仍存在争议。导致EPOR C末端缺失的突变在家族性红细胞增多症中经常被发现。与C末端区域结合的造血细胞磷酸酶可能参与EPOR功能的负调节。
