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

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.