Steel factor induces serine phosphorylation of Stat3 in human growth factor-dependent myeloid cell lines

Akihiko Gotoh, Hiroyuki Takahira, Charlie Mantel, Sara Litz-Jackson, H. Boswell, Hal Broxmeyer

Research output: Contribution to journalArticle

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Abstract

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 promotenuclear 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.

Original languageEnglish
Pages (from-to)138-145
Number of pages8
JournalBlood
Volume88
Issue number1
StatePublished - Jul 1 1996

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Phosphorylation
Stem Cell Factor
Myeloid Cells
Serine
Intercellular Signaling Peptides and Proteins
Cells
Cell Line
Interleukin-9
Tyrosine
Cytokines
Interleukin-3
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-6
DNA

ASJC Scopus subject areas

  • Hematology

Cite this

Steel factor induces serine phosphorylation of Stat3 in human growth factor-dependent myeloid cell lines. / Gotoh, Akihiko; Takahira, Hiroyuki; Mantel, Charlie; Litz-Jackson, Sara; Boswell, H.; Broxmeyer, Hal.

In: Blood, Vol. 88, No. 1, 01.07.1996, p. 138-145.

Research output: Contribution to journalArticle

Gotoh, Akihiko ; Takahira, Hiroyuki ; Mantel, Charlie ; Litz-Jackson, Sara ; Boswell, H. ; Broxmeyer, Hal. / Steel factor induces serine phosphorylation of Stat3 in human growth factor-dependent myeloid cell lines. In: Blood. 1996 ; Vol. 88, No. 1. pp. 138-145.
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