Activation of Raf/ERK1/2 MAP kinase pathway is involved in GM-CSF-induced proliferation and survival but not in erythropoietin-induced differentiation of TF-1 cells
Activation of Raf/ERK1/2 MAP kinase pathway is involved in GM-CSF-induced proliferation and survival but not in erythropoietin-induced differentiation of TF-1 cells
复制标题
DOI：
10.1016/s0898-6568(01)00201-7
复制
发表时间：
2001-10-01
影响因子：
4.8
通讯作者：
Magócsi, M
中科院分区：
文献类型：
--
作者：
Kolonics, A;Apáti, A;Magócsi, M
通过比较Epo- r异常的人因子依赖性骨髓样TF-1细胞的Epo和GM-CSF信号，研究MAPK通路在分化、增殖和存活中的作用。GM-CSF戒断诱导细胞周期阻滞和凋亡，并伴有caspase-3活性升高、DNA降解和抗凋亡Bcl-2和Bcl-xl蛋白表达降低。再给药GM-CSF但作为Epo逆转这些过程并诱导增殖。GM-CSF促进细胞存活和增殖与MEK-1依赖性ERK1/2、Elk-1和CREB磷酸化、Egr-1、c-Fos表达以及STAT-5、AP-1、c-Myb和NF-kappaB dna结合增加相关。相比之下，Epo不能激活Raf-1/ERK1/2 MAPK通路，也不能诱导Egr-1和/或c-Fos的表达，而在gm - csf缺失的细胞中，它能诱导红系分化。此外，在GM-CSF的存在下，epo诱导的血红蛋白产生被抑制。这些结果表明，MAPK级联的激活对于epo诱导的TF-1细胞的血红蛋白生成并不是必需的，并且表明gm - csf刺激的细胞增殖信号与epo诱导的红细胞分化之间存在负交叉。(C) 2001爱思唯尔科学公司版权所有。
The involvement of MAPK pathways in differentiation, proliferation and survival was investigated by comparing Epo and GM-CSF signalling in human factor-dependent myeloerythroid TF-1 cells with abnormal Epo-R. GM-CSF withdrawal induced cell-cycle arrest and apoptosis accompanied by increased caspase-3 activity, DNA degradation and reduced expression of the antiapoptotic Bcl-2 and Bcl-xl proteins. Readministration of GM-CSF but act Epo reversed these processes and induced proliferation. The GM-CSF promoted cell survival and proliferation correlated with MEK-1 dependent ERK1/2, Elk-1 and CREB phosphorylation and Egr-1, c-Fos expression as well as with increased STAT-5, AP-1, c-Myb and NF-kappaB DNA-binding. In contrast, Epo failed to activate the Raf-1/ERK1/2 MAPK pathway or to induce Egr-1 and/or c-Fos expression, while it induced erythroid differentiation in GM-CSF-deprived cells. In addition, the Epo-induced haemoglobin production was inhibited in the presence of GM-CSF. These results demonstrate that the activation of MAPK cascade is not necessary for Epo-induced haemoglobin production in TF-1 cells and suggest a negative cross-talk between the signalling of GM-CSF-stimulated cell proliferation and Epo-induced erythroid differentiation. (C) 2001 Elsevier Science Inc. All rights reserved.