Steel factor induces serine phosphorylation of Stat3 in human growth factor-dependent myeloid cell lines.
Steel factor (SLF) acts synergistically with various hematopoietic growth factors that use the Jak-Stat pathways in vivo and in vitro, although the contribution by SLF to this pathway is unknown. We show here that SLF induces time- and dose-dependent phosphorylation of Stat3 in the human growth factor-dependent cell lines MO7e and TF-1. This phosphorylation occurs exclusively on serine residues. Simultaneous stimulation with SLF plus other cytokines that induce tyrosine phosphorylation of Stat3, such as interleukin-9 (IL-9) in MO7e cells or IL-6 in TF-1 cells, resulted in tyrosine phosphorylation and enhanced serine phosphorylation of Stat3. Serine phosphorylation alone did not promote nuclear translocation or DNA binding activity to the sis-inducible element of Stat3. However, costimulation with SLF plus IL-9 in MO7e cells resulted in the nuclear translocation of serine-hyperphosphorylated Stat3. Serine phosphorylation of Stat3 was also observed by the stimulation of cells with granulocyte-macrophage colony-stimulating factor and IL-3, which do not induce tyrosine phosphorylation of Stat3. These results suggest that SLF might modulate the Jak-Stat3 pathway by serine phosphorylation and that the Jak-Stat pathway may be differentially regulated by the combinational stimulation of two or more cytokines.
Gotoh
A
A
Department of Medicine and Microbiology/Immunology Indiana University School of Medicine, Indianapolis, 46202-5121, USA.
Takahira
H
H
Mantel
C
C
Litz-Jackson
S
S
Boswell
H S
HS
Broxmeyer
H E
HE
D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016298:Hematopoietic Cell Growth Factors / Q000502:physiology; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D007947:Leukemia, Megakaryoblastic, Acute / Q000473:pathology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis*; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D004268:DNA-Binding Proteins; D016298:Hematopoietic Cell Growth Factors; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D019089:Stem Cell Factor; D015534:Trans-Activators; D010768:Phosphoserine