Tyrosine Phosphorylation of DNA Binding Proteins by Multiple Cytokines

Abstract

Interferon-α (IFN-α) and IFN-γ regulate gene expression by tyrosine phosphorylation of several transcription factors that have the 91-kilodalton (p91) protein of interferon-stimulated gene factor-3 (ISGF-3) as a common component. Interferon-activated protein complexes bind enhancers present in the promoters of early response genes such as the high-affinity Fcγ receptor gene (FcγRI). Treatment of human peripheral blood monocytes or basophils with interleukin-3 (IL-3), IL-5, IL-10, or granulocyte-macrophage colony-stimulating factor (GM-CSF) activated DNA binding proteins that recognized the IFN-γ response region (GRR) located in the promoter of the FcγRI gene. Although tyrosine phosphorylation was required for the assembly of each of these GRR binding complexes, only those formed as a result of treatment with IFN-γ or IL-10 contained p91. Instead, complexes activated by IL-3 or GM-CSF contained a tyrosine-phosphorylated protein of 80 kilodaltons. Induction of FcγRI RNA occurred only with IFN-γ and IL-10, whereas pretreatment of cells with GM-CSF or IL-3 inhibited IFN-γ induction of FcγRI RNA. Thus, several cytokines other than interferons can activate putative transcription factors by tyrosine phosphorylation.

Keywords

Affiliated Institutions

• Center for Biologics Evaluation and Research US

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