Distinct signaling from stem cell factor and erythropoietin in HCD57 cells
Distinct signaling from stem cell factor and erythropoietin in HCD57 cells
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DOI：
10.1074/jbc.272.11.6850
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发表时间：
1997-03-14
影响因子：
4.8
通讯作者：
Sawyer, ST
中科院分区：
文献类型：
--
作者：
JacobsHelber, SM;Penta, K;Sawyer, ST
最近的一份报告（Wu， H, Klingmuller， U, Besmer， P, and Lodish， H， F. (1995) Nature 377, 242-246）记录了促红细胞生成素（EPO）受体（EPOR）与干细胞因子（SCF）受体（c-KIT）的相互作用，并表明SCF通过EPOR起作用。为了阐明SCF影响促红细胞生成素信号通路的能力，我们研究了SCF对EPOR依赖性HCD57细胞中EPOR磷酸化、SHC/ERK-1活性以及细胞增殖和凋亡的影响。SCF处理这些细胞导致EPOR磷酸化，然而，SCF依赖性EPOR磷酸化不会启动类似EPOR的细胞内信号。SCF诱导细胞增殖、SHC磷酸化和ERK-1活化，但不激活JAK/STAT通路。在EPOR下调的细胞中，SCF刺激了独立于EPOR的SHC磷酸化和ERK-1激活；EPOR的存在似乎促进了SCF活化SHC和ERK-1。此外，用SCF处理HCD57细胞在3天内增加了细胞数量，但在这些细胞中观察到凋亡。这些数据可能说明了红细胞对EPO的增殖和防止凋亡的两种不同途径，从而提供了一种区分这些细胞内信号的系统。
A recent report (Wu, H,, Klingmuller, U., Besmer, P., and Lodish, H, F. (1995) Nature 377, 242-246) documents the interaction of the erythropoietin (EPO) receptor (EPOR) with the stem cell factor (SCF) receptor (c-KIT) and suggests that SCF acts through the EPOR. To elucidate the ability of SCF to affect the erythropoietin signaling pathway, we studied the effect of SCF on EPOR phosphorylation, SHC/ERK-1 activity, and cell proliferation and apoptosis in EPO-dependent HCD57 cells, Treatment of these cells with SCF resulted in phosphorylation of the EPOR, However, SCF-dependent phosphorylation of the EPOR did not initiate an EPO-like intracellular signal. SCF induced proliferation, SHC phosphorylation, and activation of ERK-1 but did not activate the JAK/STAT pathway. SCF stimulated SHC phosphorylation and ERK-1 activation independent of the EPOR in cells where the EPOR was down-regulated; the presence of the EPOR appeared to facilitate SCF activation of SHC and ERK-1. Furthermore, treatment of HCD57 cells with SCF increased cell number over a 3-day treatment, but apoptosis was observed in these cells. These data may illustrate two distinct pathways for erythroid cell proliferation and prevention of apoptosis in response to EPO, thereby providing a system to discriminate these intracellular signals.