Lee Younghee, Broxmeyer Hal E, Mantel Charlie, Kwon Hyung-Joo, Kim Jae Wha, Kim Jin Sook, Kwon Durhan, Choe In Seong
Cell Biology Laboratory, Korea Research Institute of Bioscience and Biotechnology (KRIBB), P.O. Box 115, Yusong, Daejon 305-600, Korea.
Exp Mol Med. 2003 Jun 30;35(3):222-6. doi: 10.1038/emm.2003.30.
Stem cell factor (SCF) is an early-acting cytokine inducing proliferative synergy with other cytokines in hematopoietic cells. We earlier showed that p21 was synergistically induced in SCF synergy and the p44/42 MAPK pathway was essential for the transcriptional control of p21. SCF synergy accompanies protein synthesis. p70S6K implicated in translational control in many other systems has not been shown in SCF synergy induced system. GM-CSF dependent human cell line MO7e was stimulated with GM-CSF with SCF, and investigated activation of p70S6K by using phospho-specific antibody. A possible contribution of p70S6K to SCF synergy was examined by measuring p21 induction as a model system. p70S6K was slightly activated by GM-CSF alone and markedly activated by SCF alone. Combined stimulation with these two cytokines synergistically activated p70S6K resulting in persistent activation. Addition of the pathway-specific inhibitors for P13K or FRAP/TOR, two up-stream pathways of p70S6K resulted in abolishment of p70S6K phosphorylation and also significant reduction of p21 protein level. These data suggest that synergistically activated p70S6K by GM-CSF plus SCF involves, at least in part, protein translational control including regulation of p21 protein.
干细胞因子（SCF）是一种早期作用的细胞因子，可诱导造血细胞与其他细胞因子产生增殖协同作用。我们先前表明，p21在SCF协同作用中被协同诱导，且p44/42 MAPK途径对于p21的转录调控至关重要。SCF协同作用伴随着蛋白质合成。在许多其他系统中参与翻译控制的p70S6K在SCF协同诱导系统中尚未见报道。用GM-CSF和SCF刺激GM-CSF依赖的人细胞系MO7e，并使用磷酸化特异性抗体研究p70S6K的激活情况。通过测量p21诱导作为模型系统，研究了p70S6K对SCF协同作用的可能贡献。单独使用GM-CSF可使p70S6K轻微激活，单独使用SCF可使其显著激活。这两种细胞因子联合刺激可协同激活p70S6K，导致持续激活。添加p70S6K的两条上游途径P13K或FRAP/TOR的途径特异性抑制剂，会导致p70S6K磷酸化的消除以及p21蛋白水平的显著降低。这些数据表明，GM-CSF加SCF协同激活的p70S6K至少部分涉及蛋白质翻译控制，包括对p21蛋白的调控。
