Functional Involvement of PTP-U2L in Apoptosis Subsequent to Terminal Differentiation of Monoblastoid Leukemia Cells*-猫眼课题宝

PTP-U2L 在单母细胞白血病细胞终末分化后的细胞凋亡中的功能参与*

DOI：

10.1074/jbc.273.33.21187

发表时间：

1998

期刊：

The Journal of Biological Chemistry

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

H. Seimiya;T. Tsuruo

蛋白质酪氨酸磷酸酶（PTPs）的大家族通过逆转源自蛋白质酪氨酸激酶的作用的激动性或拮抗性磷酸化事件来双向调节细胞内信号传导途径。受体样PTPPTP-U2在佛波酯诱导的单核细胞白血病U937细胞分化过程中表达我们发现，较短的异构体，PTP-U2 S，表达在分化过程中的早期阶段和较长的异构体，PTP-U2 L，诱导在较晚的阶段。在12-O-十四酰基佛波醇-13-乙酸酯的存在下，PTP-U2 L在U937细胞中的异位表达增强了终末分化细胞的几个特征。最引人注目的是PTP-U2 L促进分化细胞的凋亡，这仅被半胱天冬酶抑制剂Z-Asp-CH 2-DCB部分抑制。催化失活的突变体PTP-U2 L（C → S）仍然保留了增强分化的能力，但保留了在较小程度上增强随后细胞凋亡的能力。这些数据表明PTP-U2 L在U937细胞终末分化后的凋亡中的功能参与。由于终末分化的血细胞经常发生凋亡，数据还表明PTP-U2 L可能参与体内造血细胞的生理更新。

A large family of protein tyrosine phosphatases (PTPs) bidirectionally regulate intracellular signaling pathways by reversing agonistic or antagonistic phosphorylation events derived from the action of protein tyrosine kinases. Receptor-like PTPPTP-U2 is expressed during phorbol ester-induced differentiation of monoblastoid leukemia U937 cells. We found that the shorter isoform, PTP-U2S, was expressed at an earlier phase in the course of differentiation and the longer isoform, PTP-U2L, was induced at a later phase. In the presence of 12-O-tetradecanoylphorbol-13-acetate, ectopic expression of PTP-U2L in U937 cells enhanced several characteristics of terminally differentiated cells. Most striking was that PTP-U2L enhanced apoptosis of the differentiated cells, which was only partially inhibited by caspase inhibitor Z-Asp-CH2-DCB. The catalytically inactive mutant PTP-U2L(C → S) still retained the ability to enhance the differentiation but retained the ability to enhance the following apoptosis of the cells to a lesser extent. These data indicate a functional involvement of PTP-U2L in apoptosis subsequent to terminal differentiation of U937 cells. Since terminally differentiated blood cells often undergo apoptosis, the data also suggest that PTP-U2L might be involved in physiological turnover of hematopoietic cells in vivo.