Woldman I, Mellitzer G, Kieslinger M, Buchhart D, Meinke A, Beug H, Decker T
Vienna Biocenter, Institute of Microbiology and Genetics, Austria.
J Immunol. 1997 Jul 15;159(2):877-86.
We have investigated the activation of the STAT5 protein during the differentiation of myelomonocytic cells. In the human U937 promonocytic cell line, STAT5 activation occurred in response to several inducers of monocytic differentiation (phorbol ester, 1alpha,25-dihydroxyvitamin D3, and retinoic acid). In the promyelocytic HL60 cell line, STAT5 was activated in the course of either phorbol ester-induced monocytic differentiation or DMSO-induced granulocytic differentiation. To test for involvement of STAT5 in the differentiation of primary nonimmortalized cells, chicken myeloid progenitor cells transfected with the ts21-E26 avian retrovirus were studied. At 37 degrees C the temperature-sensitive oncoprotein of the ts21-E26 virus (p135(gag-myb-ets)) installs a differentiation block that is released by a shift to the nonpermissive temperature (42 degrees C). Both proliferation and differentiation of ts21-E26-transfected myeloblasts require the continuous presence of chicken myelomonocytic growth factor (cMGF). Addition of cMGF to growth factor-starved cells rapidly caused STAT5 tyrosine phosphorylation, DNA binding, and transcriptional activity at both permissive and nonpermissive temperatures. Moreover, the temperature shift-induced onset of myelomonocytic differentiation strictly correlated with the appearance of activated STAT5 in ts21-E26-infected myeloblasts, but not in cells infected with wtE26 retrovirus. These data position STAT5 in a nuclear signaling cascade induced by the cMGF receptor and suggest a contribution of STAT5 to the process of myelomonocytic differentiation or to the functional changes that accompany the maturation of myeloid progenitor cells to a terminally differentiated stage.
我们研究了骨髓单核细胞分化过程中STAT5蛋白的激活情况。在人U937前单核细胞系中，STAT5激活是对几种单核细胞分化诱导剂（佛波酯、1α,25 - 二羟基维生素D3和视黄酸）的响应。在早幼粒细胞HL60细胞系中，STAT5在佛波酯诱导的单核细胞分化或二甲基亚砜诱导的粒细胞分化过程中被激活。为了检测STAT5是否参与原代未永生化细胞的分化，研究了用ts21 - E26禽逆转录病毒转染的鸡骨髓祖细胞。在37℃时，ts21 - E26病毒的温度敏感型癌蛋白（p135(gag - myb - ets)）会导致分化阻滞，而将温度转变为非允许温度（42℃）可解除这种阻滞。ts21 - E26转染的成髓细胞的增殖和分化都需要持续存在鸡骨髓单核细胞生长因子（cMGF）。在允许温度和非允许温度下，向缺乏生长因子的细胞中添加cMGF都会迅速引起STAT5酪氨酸磷酸化、DNA结合及转录活性。此外，温度转变诱导的骨髓单核细胞分化的起始与ts21 - E26感染的成髓细胞中活化STAT5的出现严格相关，但在野生型E26逆转录病毒感染的细胞中则不然。这些数据表明STAT5处于由cMGF受体诱导的核信号级联反应中，并提示STAT5对骨髓单核细胞分化过程或对骨髓祖细胞成熟至终末分化阶段所伴随的功能变化有贡献。
