PMID:10336453

Citation	Yamaguchi, T, Mukasa, T, Uchida, E, Kanayasu-Toyoda, T and Hayakawa, T (1999) The role of STAT3 in granulocyte colony-stimulating factor-induced enhancement of neutrophilic differentiation of Me2SO-treated HL-60 cells. GM-CSF inhibits the nuclear translocation of tyrosine-phosphorylated STAT3. J. Biol. Chem. 274:15575-81
Abstract	The role of granulocyte colony-stimulating factor (G-CSF) on neutrophilic differentiation of Me2SO-treated HL-60 cells was studied. G-CSF augmented the functional maturation of Me2SO-treated HL-60 cells in terms of both O-2-generating ability and expression of the formyl-methionyl-leucyl-phenylalanine receptor. G-CSF induced enhancement of cell growth in Me2SO-treated HL-60 cells. These results indicate that G-CSF is a potent enhancer for the differentiation and proliferation of Me2SO-treated HL-60 cells. G-CSF caused the activation of p70 S6 kinase but not mitogen-activated protein (MAP) kinase. On the other hand, G-CSF rapidly induced tyrosine phosphorylation of signal transducers and activators of transcription-3 (STAT3), but did not induce serine727 phosphorylation. From the analysis of confocal laser scanning fluorescence microscopy and differential centrifugation, it was clearly demonstrated that G-CSF induced nuclear translocation of tyrosine-phosphorylated STAT3. The G-CSF-dependent enhancement of neutrophilic differentiation in Me2SO-HL-60 cells was reversely inhibited by granulocyte-macrophage colony-stimulating factor (GM-CSF). Notably, in the presence of GM-CSF, G-CSF induced the tyrosine phosphorylation of STAT3 but failed to induce the nuclear translocation of tyrosine-phosphorylated STAT3. GM-CSF induced activation of not only p70 S6 kinase, but also of MAP kinase. Furthermore, GM-CSF caused the rapid serine727 phosphorylation of STAT3, both in the presence and absence of G-CSF. PD98059, an MEK1 inhibitor, inhibited the G-CSF-dependent serine727 phosphorylation of STAT3 and blocked the inhibitory effect of GM-CSF on G-CSF-dependent nuclear translocation of STAT3. These results suggest that G-CSF-dependent nuclear translocation of STAT3 coordinates with the promotion of neutrophilic differentiation in Me2SO-treated HL-60 cells.
Links	PubMed
Keywords	Calcium-Calmodulin-Dependent Protein Kinases/metabolism; Cell Differentiation/drug effects; Cell Division/drug effects; DNA-Binding Proteins/metabolism; Dimethyl Sulfoxide; Enzyme Activation/drug effects; Flavonoids/pharmacology; Fluorescent Antibody Technique; Granulocyte Colony-Stimulating Factor/pharmacology; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology; HL-60 Cells/drug effects; Humans; Phosphotyrosine/analysis; Ribosomal Protein S6 Kinases/metabolism; STAT3 Transcription Factor; Signal Transduction/drug effects; Trans-Activators/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:MAP4		GO:0032604: granulocyte macrophage colony-stimulating factor production	ECO:0000314:		P		Figure 4	complete CACAO 6120
HUMAN:STAT3	part_of	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete

References

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