title: Synergistic activation of p70S6 kinase associated with stem cell factor in MO7e cells.
abstract: 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.
authors.affiliation: Cell Biology Laboratory, Korea Research Institute of Bioscience and Biotechnology (KRIBB), P.O. Box 115, Yusong, Daejon 305-600, Korea.
authors.forename: Younghee
authors.initials: Y
authors.lastname: Lee
authors.forename: Hal E
authors.initials: HE
authors.lastname: Broxmeyer
authors.forename: Charlie
authors.initials: C
authors.lastname: Mantel
authors.forename: Hyung-Joo
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Jae Wha
authors.initials: JW
authors.lastname: Kim
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kim
authors.forename: Durhan
authors.initials: D
authors.lastname: Kwon
authors.forename: In Seong
authors.initials: IS
authors.lastname: Choe
mesh_terms: D004357:Drug Synergism; D004789:Enzyme Activation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019089:Stem Cell Factor / Q000494:pharmacology*; D022061:Tacrolimus Binding Protein 1A / Q000378:metabolism; D054462:p21-Activated Kinases
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D019089:Stem Cell Factor; D022061:Tacrolimus Binding Protein 1A; D054462:p21-Activated Kinases