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Synergistic activation of p70S6 kinase associated with stem cell factor in MO7e cells
YoungheeLee,HalE.Broxmeyer,CharlieMantel,Hyung-JooKwon,JaeWhaKim,JinSookKim,DurhanKwon,InSeongChoe 생화학분자생물학회 2003 Experimental and molecular medicine Vol.35 No.3
Stem cel factor (SCF) is an early-acting cytokine inducing proliferative synergy with other cytokines in hematopoietic cels. We earlier showed that p21 was synergisticaly induced in SCF synergy and the p44/42 MAPK pathway was essential for the transcriptional control of p21. SCF synergy accom-panies protein synthesis. p70S6K implicated in translational control in many other systems has not been shown in SCF synergy induced system. ulated with GM-CSF with SCF, and investigated ac-tivation of p70S6K by using phospho-specific anti-body. A possible contribution of p70S6K to SCF synergy was examined by measuring p21 induc-tion as a model system. p70S6K was slightly acti-vated by GM-CSF alone and markedly activated by SCF alone. Combined stimulation with these two cytokines synergisticaly activated p70S6K resulting in persistent activation. Adition of the pathway- specific inhibitors for PI3K or FRAP/TOR, two up-stream pathways of p70S6K resulted in abolish-ficant reduction of p21 protein level. These data sugest that synergisticaly activated p70S6K by GM-CSF plus SCF involves, at least in part, protein translational control including regulation of p21 protein.