Transcriptional induction of pim-1 protein kinase gene expression by interferon γ and posttranscriptional effects on costimulation with steel factor

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65 Scopus citations

Abstract

Steel factor (SLF) synergizes with interferon γ (IFNγ) to stimulate proliferation of the human factor-dependent cell line MO7e. We examined the effects of IFNγ and SLF treatment, alone or in combination, on the expression of a 33-kD cytoplasmic protein serine/threonine kinase designated pim-1 whose expression has been closely associated with proliferation induced by related myeloid cytokines. IFNγ alone, but not SLF, stimulated expression of pim-1 RNA and protein in MO7e cells; compared with IFNγ alone, costimulation with IFNγ and SLF resulted in a twofold to threefold increase in pim-1 message and protein expression, correlating with synergistic effects on cell proliferation. Both IFNγ and IFNγ/SLF induced pim-1 mRNA in the absence of de novo protein synthesis. Nuclear run-on assays showed that, although IFNγ alone increased the rate of pim-1 gene transcription, costimulation with IFNγ and SLF did not further potentiate this effect; however, the stability of pim-1 message was significantly enhanced in the presence of both cytokines. An IFNγ-responsive element within the 5' flanking region of the pim-1 gene that could confer IFNγ responsiveness on a heterologous promoter was identified. This sequence, designated PMGAS, formed a specific complex with Stat (signal transducers and activators of transcription) 1 α (the p91 subunit of the transcription factor ISGF3 [interferon-stimulated gene factor 3]) in IFNγ-treated cell extracts, suggesting that the transcriptional effects of IFNγ on pim-1 expression may be mediated by Stat 1α.

Original languageEnglish (US)
Pages (from-to)3494-3502
Number of pages9
JournalBlood
Volume85
Issue number12
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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