Tauchi T, Feng G S, Shen R, Hoatlin M, Bagby G C, Kabat D, Lu L, Broxmeyer H E
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202.
J Biol Chem. 1995 Mar 10;270(10):5631-5. doi: 10.1074/jbc.270.10.5631.
Erythropoietin (Epo) regulates the proliferation and differentiation of erythroid precursors. The phosphorylation of proteins at tyrosine residues is critical in the growth signaling induced by Epo. This mechanism is regulated by the activities of both protein-tyrosine kinases and protein tyrosine phosphatases. The discovery of phosphotyrosine phosphatases that contain SH2 domains suggests roles for these molecules in growth factor signaling pathways. We found that Syp, a phosphotyrosine phosphatase, widely expressed in all tissues in mammals became phosphorylated on tyrosine after stimulation with Epo in M07ER cells engineered to express high levels of human EpoR. Syp was complexed with Grb2 in Epo-stimulated M07ER cells. Direct binding between Syp and Grb2 was also observed in vitro. Furthermore, Syp appeared to bind directly to tyrosine-phosphorylated EpoR in M07ER cells. Both NH2-terminal and COOH-terminal SH2 domains of Syp, made as glutathione S-transferase fusion proteins, were able to bind to the tyrosine-phosphorylated EpoR in vitro. These results suggest that Syp may be an important signaling component downstream of the EpoR and may regulate the proliferation and differentiation of hematopoietic cells.
促红细胞生成素（Epo）调节红系前体细胞的增殖和分化。蛋白质酪氨酸残基的磷酸化在Epo诱导的生长信号传导中至关重要。这一机制受蛋白质酪氨酸激酶和蛋白质酪氨酸磷酸酶的活性调节。含有SH2结构域的磷酸酪氨酸磷酸酶的发现表明这些分子在生长因子信号通路中发挥作用。我们发现，在经过基因改造以高水平表达人EpoR的M07ER细胞中，用Epo刺激后，在哺乳动物所有组织中广泛表达的磷酸酪氨酸磷酸酶Syp在酪氨酸上发生了磷酸化。在Epo刺激的M07ER细胞中，Syp与Grb2形成复合物。在体外也观察到Syp与Grb2之间的直接结合。此外，在M07ER细胞中，Syp似乎直接与酪氨酸磷酸化的EpoR结合。作为谷胱甘肽S-转移酶融合蛋白制备的Syp的NH2末端和COOH末端SH2结构域在体外均能够与酪氨酸磷酸化的EpoR结合。这些结果表明，Syp可能是EpoR下游的一个重要信号成分，并且可能调节造血细胞的增殖和分化。
