Colony-stimulating factors and interferon-gamma activate a protein related to MGF-Stat 5 to cause formation of the differentiation-induced factor in myeloid cells.
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-gamma (IFN-gamma) 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-gamma. 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-gamma-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.
Barahmand-pour
F
F
Vienna Biocenter, Institute of Microbiology and Genetics, Austria.
Meinke
A
A
Eilers
A
A
Gouilleux
F
F
Groner
B
B
Decker
T
T
D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D006801:Humans; D007106:Immune Sera; D007371:Interferon-gamma / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D008894:Milk Proteins; D009841:Oligonucleotides; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D007106:Immune Sera; D008894:Milk Proteins; D009841:Oligonucleotides; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor