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 (MCF-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.