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 PI3K or FRAP/TOR, two upstream 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.
1-Phosphatidylinositol 3-Kinase/metabolism ; Drug Synergism ; Enzyme Activation ; Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology ; Hematopoietic Stem Cells/*enzymology ; Human ; Phosphorylation/drug effects ; Protein-Serine-Threonine Kinases/metabolism ; Ribosomal Protein S6 Kinases, 70kD/antagonists & inhibitors/*metabolism ; Stem Cell Factor/*pharmacology ; Tacrolimus Binding Protein 1A/metabolism