The SH2 domain-containing protein tyrosine phosphatase SHP-1 is induced by granulocyte colony-stimulating factor (G-CSF) and modulates signaling from the G-CSF receptor.
The SH2 domain-containing protein tyrosine phosphatase SHP-1 is induced by granulocyte colony-stimulating factor (G-CSF) and modulates signaling from the G-CSF receptor.
复制标题
含有 SH2 结构域的蛋白酪氨酸磷酸酶 SHP-1 由粒细胞集落刺激因子 (G-CSF) 诱导，并调节来自 G-CSF 受体的信号传导。
DOI：
10.1038/sj.leu.2401822
复制
发表时间：
2000
期刊：
影响因子：
11.4
通讯作者：
Touw,IP
中科院分区：
文献类型：
--
作者：
Ward,AC;Oomen,SP;Smith,L;Gits,J;vanLeeuwen,D;Soede-Bobok,AA;Erpelinck-Verschueren,CA;Yi,T;Touw,IP
含SH 2结构域的蛋白酪氨酸磷酸酶SHP-1在造血系统中广泛表达。SHP-1已显示通过直接对接到受体本身或酪氨酸激酶的Jak家族的成员（其本身是受体复合物的一部分）来负控制来自许多细胞因子受体的信号转导。缺乏SHP-1的飞蛾和存活的飞蛾小鼠具有增加的骨髓生成，并显示形态学和表型上不成熟的粒细胞的积累，表明SHP-1在粒细胞分化中的作用。在这里，我们报告说，SHP-1蛋白水平上调粒细胞集落刺激因子（G-CSF）介导的粒细胞分化的髓系32 D细胞。SHP-1在这些细胞中的强制表达导致增殖降低和分化增强，而引入催化失活突变体产生增殖增加并导致分化延迟。体外结合实验表明，SHP-1的SH 2结构域不能直接与酪氨酸磷酸化的G-CSF受体（G-CSF-R）结合。此外，SHP-1在表达缺乏所有胞质酪氨酸的G-CSF-R突变体的Ba/F3细胞中的过表达也抑制增殖。总之，这些数据表明，SHP-1通过不需要与活化的G-CSF-R对接的机制直接调节造血细胞中G-CSF介导的应答。
The SH2 domain-containing protein tyrosine phosphatase SHP-1 is expressed widely in the hematopoietic system. SHP-1 has been shown to negatively control signal transduction from many cytokine receptors by direct docking to either the receptor itself, or to members of the Jak family of tyrosine kinases which are themselves part of the receptor complex. Motheaten and viable motheaten mice, which are deficient in SHP-1, have increased myelopoiesis and show an accumulation of morphologically and phenotypically immature granulocytes, suggesting a role for SHP-1 in granulocytic differentiation. Here, we report that SHP-1 protein levels are up-regulated during the granulocyte colony-stimulating factor (G-CSF)-mediated granulocytic differentiation of myeloid 32D cells. Enforced expression of SHP-1 in these cells leads to decreased proliferation and enhanced differentiation, while introduction of a catalytically inactive mutant produces increased proliferation and results in a delay of differentiation. In vitro binding revealed that the SH2 domains of SHP-1 are unable to associate directly with tyrosine-phosphorylated G-CSF receptor (G-CSF-R). Furthermore, over-expression of SHP-1 in Ba/F3 cells expressing a G-CSF-R mutant lacking all cytoplasmic tyrosines also inhibited proliferation. Together, these data suggest that SHP-1 directly modulates G-CSF-mediated responses in hematopoietic cells via a mechanism that does not require docking to the activated G-CSF-R.