PIM-1 LEVELS DETERMINE THE SIZE OF EARLY B-LYMPHOID COMPARTMENTS IN BONE-MARROW
PIM-1 LEVELS DETERMINE THE SIZE OF EARLY B-LYMPHOID COMPARTMENTS IN BONE-MARROW
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DOI：
10.1084/jem.178.5.1665
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发表时间：
1993-11-01
影响因子：
15.3
通讯作者：
BERNS, A
中科院分区：
文献类型：
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作者：
DOMEN, J;VANDERLUGT, NMT;BERNS, A
小鼠原癌基因Pim-1编码两种细胞质丝氨酸-苏氨酸特异性蛋白激酶，在小鼠白血病病毒诱导的造血肿瘤中经常被前病毒插入激活。过表达Pim-1的转基因小鼠自发性T细胞淋巴瘤发病率低，而无突变小鼠缺乏明显的表型。我们分析了零突变和Emu-Pim-1转基因小鼠的早期B淋巴细胞室。Pim-1的表达水平似乎是这些细胞对生长因子白介素7 （IL-7）和钢铁因子（SF）的反应能力的决定因素。零突变小鼠的反应受损可以通过引入功能性的Pim-1转基因来恢复。此外，Pim-1的过表达促进了依赖于IL-7和SF或胰岛素样生长因子1联合刺激的原始淋巴样细胞系的衍生。这些结果首次确定了Pim-1参与正常细胞功能，作为小鼠早期B淋巴生成的重要调节因子。
The mouse proto-oncogene Pim-1, which encodes two cytoplasmic serine-threonine-specific protein kinases, is frequently activated by proviral insertion in murine leukemia virus-induced hematopoietic tumors. Transgenic mice overexpressing Pim-1 show a low incidence of spontaneous T cell lymphomas, whereas null mutant mice lack an obvious phenotype. We have analyzed the early B lymphoid compartment from both null mutant and Emu-Pim-1 transgenic mice. The level of Pim-1 expression appears to be a determining factor in the ability of these cells to respond to the growth factors interleukin 7 (IL-7) and SF (steel factor). The impaired response in null mutant mice could be rescued by introduction of a functional Pim-1 transgene. Moreover, overexpression of Pim-1 facilitates the derivation of primitive lymphoid cell lines that are dependent on combined stimulation with IL-7 and SF or insulin-like growth factor 1. These results for the first time identify the involvement of Pim-1 in a normal cellular function, as an important regulator of early B lymphopoiesis in mice.