Moriggl R, Topham D J, Teglund S, Sexl V, McKay C, Wang D, Hoffmeyer A, van Deursen J, Sangster M Y, Bunting K D, Grosveld G C, Ihle J N
Howard Hughes Medical Institute, and Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Immunity. 1999 Feb;10(2):249-59. doi: 10.1016/s1074-7613(00)80025-4.
Many cytokines activate two highly homologous Stat proteins, 5a and 5b. Mice deficient in both genes lack all growth hormone and prolactin functions but retain functions associated with cytokines such as erythropoietin. Here, we demonstrate that, while lymphoid development is normal, Stat5a/b mutant peripheral T cells are profoundly deficient in proliferation and fail to undergo cell cycle progression or to express genes controlling cell cycle progression. In addition, the mice lack NK cells, develop splenomegaly, and have T cells with an activated phenotype, phenotypes seen in IL-2 receptor beta chain-deficient mice. These phenotypes are not seen in mice lacking Stat5a or Stat5b alone. The results demonstrate that the Stat5 proteins, redundantly, are essential mediators of IL-2 signaling in T cells.
许多细胞因子可激活两种高度同源的信号转导和转录激活因子（Stat）蛋白，即Stat5a和Stat5b。双基因缺陷小鼠缺乏所有生长激素和催乳素功能，但保留了与细胞因子（如促红细胞生成素）相关的功能。在此，我们证明，虽然淋巴样发育正常，但Stat5a/b突变体外周T细胞在增殖方面严重缺陷，无法进行细胞周期进程，也无法表达控制细胞周期进程的基因。此外，这些小鼠缺乏自然杀伤（NK）细胞，出现脾肿大，且具有活化表型的T细胞，这些表型在白细胞介素-2受体β链缺陷小鼠中也可见到。单独缺乏Stat5a或Stat5b的小鼠未出现这些表型。结果表明，Stat5蛋白在T细胞中是白细胞介素-2信号传导的冗余必需介质。
