Colony‐stimulating factors and interferon‐γ activate a protein related to MGF‐Stat 5 to cause formation of the differentiation‐induced factor in myeloid cells

Authors:
  • AMAndreas Meinke
    Andreas Meinke
  • AEAndreas Eilers
    Andreas Eilers
  • BGBernd Groner
    Bernd Groner
  • TDThomas Decker
    Thomas Decker
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Abstract
The Jak‐Stat pathway of intracellular signals is used by growth factor‐ and cytokine receptors to induce gene transcription. We have recently reported that differentiation of myeloid cells, induced by phorbol ester, interferon‐γ (IFN‐γ) or colony‐stimulating factor‐1 (CSF‐1) is accompanied by the activation of the differentiation‐induced factor (DIF). Activated DIF specifically associates with a subclass of gamma‐interferon activation site (GAS)‐like DNA elements. We now report that GM‐CSF, which like CSF‐1 promotes the generation of mature macrophages, activates DIF. No activation was observed after treatment with the granulocyte growth and differentiation factor G‐ CSF. Antibodies raised against a Stat family protein, designated mammary gland factor‐Stat 5 (MGF‐Stat 5), reacted with DIF induced by either CSF‐1, GM‐CSF or IFN‐γ. Antisera to other known Stats were without effect on the DIF complex in electrophoretic mobility shift assays (EMSA). A 112 kDa protein could be isolated from either GM‐CSF‐ or IFN‐γ‐treated cells by GAS oligonucleotide precipitation. This protein reacted with antibodies to both MGF‐Stat 5 and phosphotyrosine. MGF‐Stat 5 and closely related proteins thus define a subfamily of Stat transcription factors that are present in a variety of cell types and are required for the onset of immediate gene expression in response to differentiating stimuli.

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