Mice deficient for all PIM kinases display reduced body size and impaired responses to hematopoietic growth factors
Mice deficient for all PIM kinases display reduced body size and impaired responses to hematopoietic growth factors
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DOI：
10.1128/mcb.24.13.6104-6115.2004
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发表时间：
2004-07-01
影响因子：
5.3
通讯作者：
Berns, A
中科院分区：
文献类型：
--
作者：
Mikkers, H;Nawijn, M;Berns, A
原癌基因的Pim家族编码由PIM 1、PIM 2和PIM 3组成的不同类别的丝氨酸/苏氨酸激酶。尽管Pim基因在进化上高度保守，但PIM蛋白对哺乳动物发育的贡献尚不清楚。先前描述了PIM 1缺陷型小鼠，但仅表现出轻微的表型畸变。为了评估PIM蛋白在哺乳动物生理学中的作用，产生化合物Pim敲除小鼠。缺乏Pim 1、Pim 2和Pim 3表达的小鼠是可存活的和可生育的。然而，PM缺陷小鼠在出生时和整个产后生活中显示出体型的显着缩小。此外，不同造血细胞群体对生长因子的体外反应严重受损。特别地，PIM蛋白是由协同T细胞受体和白细胞介素-2信号传导介导的外周T淋巴细胞的有效增殖所必需的。这些结果表明，PIM家族的蛋白质的成员是重要的，但生长因子信号转导的抑制因子。
The Pim family of proto-oncogenes encodes a distinct class of serine/threonine kinases consisting of PIM1, PIM2, and PIM3. Although the Pim genes are evolutionarily highly conserved, the contribution of PIM proteins to mammalian development is unclear. PIM1-deficient mice were previously described but showed only minor phenotypic aberrations. To assess the role of PIM proteins in mammalian physiology, compound Pim knockout mice were generated. Mice lacking expression of Pim1, Pim2, and Pim3 are viable and fertile. However, PIM-delficient mice show a profound reduction in body size at birth and throughout postnatal life. In addition, the in vitro response of distinct hematopoietic cell populations to growth factors is severely impaired. In particular, PIM proteins are required for the efficient proliferation of peripheral T lymphocytes mediated by synergistic T-cell receptor and interleukin-2 signaling. These results indicate that members of the PIM family of proteins are important but dispensable factors for growth factor signaling.