Ihle J N, Morishita K, Bartholomew C, Matsugi T, Askew D
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
Int J Cell Cloning. 1990 Jan;8 Suppl 1:130-46. doi: 10.1002/stem.5530080712.
Interleukin 3 (IL-3) is a growth factor that supports the proliferation of early hematopoietic stem cells, as well as cells that are committed to a variety of the myeloid lineages. The mechanisms by which IL-3 functions have been studied through the use of a series of IL-3-dependent cell lines isolated from myeloid leukemias or long-term bone marrow cultures. A variety of studies have implicated tyrosine phosphorylation in IL-3 signal transduction. One of the substrates of phosphorylation is a 140 kDa, IL-3-binding protein that is speculated to be the biologically relevant IL-3 receptor. IL-3, through tyrosine phosphorylation, supports viability and growth through the regulation of transcription of a series of genes including c-myc and c-pim-1. The c-myc gene contributes to viability, in part, by regulating the transcription of the ornithine decarboxylase gene. The role of growth factors in differentiation is less clear. By studying IL-3-dependent myeloid leukemia cell lines, two genes have been identified whose altered expression is associated with blocking the ability of the cells to differentiate. The c-myb gene is a nuclear DNA binding protein that has been implicated in myeloid transformation in a number of systems. The Evi-1 gene is a novel gene of the zinc finger family of transcriptional activators. Possible mechanisms by which these genes interfere with normal differentiation are discussed.
白细胞介素3（IL-3）是一种生长因子，可支持早期造血干细胞以及多种髓系谱系细胞的增殖。通过使用从髓系白血病或长期骨髓培养物中分离出的一系列依赖IL-3的细胞系，对IL-3发挥作用的机制进行了研究。各种研究表明酪氨酸磷酸化参与了IL-3信号转导。磷酸化的底物之一是一种140 kDa的IL-3结合蛋白，推测它是生物学上相关的IL-3受体。IL-3通过酪氨酸磷酸化，通过调节包括c-myc和c-pim-1在内的一系列基因的转录来支持细胞活力和生长。c-myc基因部分通过调节鸟氨酸脱羧酶基因的转录来促进细胞活力。生长因子在分化中的作用尚不清楚。通过研究依赖IL-3的髓系白血病细胞系，已鉴定出两个基因，其表达改变与阻断细胞分化能力有关。c-myb基因是一种核DNA结合蛋白，在许多系统中都与髓系转化有关。Evi-1基因是转录激活因子锌指家族的一个新基因。讨论了这些基因干扰正常分化的可能机制。
